Finals Flashcards
Where do cells commit to a full completion?
Between G1 and S
The period between one M phase and the subsequent M phase is called:
Interphase
Which of the following processes occurs only in S phase of the cell cycle?
DNA replication
What happens during G1 in the cell cycle of a proliferating cell?
The cell makes more proteins, lipids, etc. and grows in size
Cyclins are needed to activate Cdks, but Cdk activity is not directly correlated with cyclin levels. Why?
Cdks are also regulated by phosphorylation.
Levels of M-cyclins rapidly drop towards the end of mitosis, so that the M-Cdk becomes inactive. What is the cause for this dramatic decrease in cyclin expression?
Increased rate of protein degradation
Platelet-derived growth factor (PDGF) is a mitogen that activates tyrosine kinase receptors and this leads to the proliferation of cells. Signaling downstream from the PDGF receptor does what to stimulate proliferation?
Phosphorylates the Rb protein to relieve inhibition of cell proliferation genes
The cell-cycle control system uses Cdk inhibitor proteins:
To arrest the cell cycle at specific transition points.
The protein p53 is an important tumor suppressor that arrests the cell cycle if DNA is damaged. P53 functions by
Turning on the transcription of a protein that binds to and inhibits Cdks.
Which statement is true about M-Cdks?
Activation of M-Cdk determines if/when M phase is initiated.
Why is cell division important?
Reproduction, development of multicellular organism, cell replacement (injured or worn out cells)
What happens in mitosis?
Nuclear division
What happens in cytokinesis?
Cytoplasmic division
What happens in G1?
Some growth (non dividing cells will revert to G0)
What happens in S?
DNA replication
What happens in G2?
Growth
What is MPF?
Cyclin-Cdl complex
What might lead to increased levels of cyclin?
Increased levels of transcription/translation or decreased degradation
How might the rapid decrease in cyclin be accomplished?
Ubiquitin addition and degradation by proteasomes
Why doesn’t MPF activity mirror changes in cyclin levels?
Has to be phosphorylated correctly
What are questions at G2 checkpoint?
Is all DNA replicated? Is all DNA damage repaired
What are questions in mitosis checkpoint?
Are all chromosomes attached to mitotic spindle?
What are questions in G1 checkpoint?
Is environment favorable for S phase?
What is inhibition between G2 and M?
Inhibition of activating phosphatase (Cdc25) blocks entry to mitosis
What is inhibition in M?
Inhibition of APC activation delays exit from mitosis
What is inhibition in G1?
Idk inhibitors block entry into S phase
What does MPF/CDK phosphorylate to cause mitosis?
- ) Formation of mitotic spindle: MAPS change microtubule dynamics
- ) Condensation of DNA: histones compact chromosomes
- ) Breakdown of nuclear membrane: lamins disassemble nuclear lamina
- ) Activate other signal pathways: kinases cause downstream changes in other protein changes
What happens if you go through cell cycle with DNA damage?
Increase chance of cell death and mutations lead to cancer
When do cell cycle checkpoints halt cell progress?
If certain processes are incomplete or chromosomal DNA is damaged
What is the process of checkpoint control?
- ) Sensor detects abnormalities
- ) Info transmitted by signal
- ) Signal-activated effector inhibits cell cycle
The five stages of mitosis occur in which order?
Prophase, prometaphase, metaphase, anaphase, telophase
In the cell cycle, duplication of the centrosome begins in:
S phase
The mitotic spindle is made of:
Microtubules
In the cell cycle, the mitotic spindle begins to assemble in:
Prophase
Microtubules capture chromosomes by binding to:
Kinetochores on the sister chromatids.
By which of the following processes do microtubules and chromosomes in animal cells “find” and then bind to each other during mitosis?
Microtubules extend and retract from the spindle poles by dynamic instability, until they randomly contact the chromosome kinetochores.
The anaphase-promoting complex (APC) triggers the onset of anaphase by:
Triggering the destruction of the cohesins that hold the sister chromatids together.
How are chromosomes held at the metaphase plate before anaphase?
There is tension on the chromosomes, with pulling forces towards each spindle pole
Which of the following contribute to the separation of sister chromatids at the end of metaphase and during anaphase?
Sliding of interpolar microtubules to push poles apart, degradation of cohesins, proteins that hold sister chromatids together, shortening of kinetochore microtubules, and motor proteins
Describe what the outcome for a cell would be for each of the following, in comparison to the parent cell:
A. Cell cycle is completed except for cytokinesis?
B. Cell cycles consisting of S phase and M phase only?
C. Cell cycle stopped in G1
A. One cell with two nuclei, instead of one
B. With continued S and M phases, you would replicate the cells, but without G phases, where growth can occur, the cells would get progressively smaller
C. Would be similar to the “parent” cell (although basically would be the parent cell). Depending on where in G1, you could also say that there would be growth so the cell might be larger.
You have isolated a strain of mutant yeast cells that divides normally at 30°C but cannot enter M phase at 37°C. You have isolated its mitotic cyclin and mitotic Cdk and find that both are normal and can form a normal M-Cdk complex at both temperatures. Which of the following temperature-sensitive mutations could be responsible for the behavior of this strain of yeast?
Inactivation of a phosphatase that acts on the Cdk kinase and a decrease in the levels of a transcriptional regulator required for producing sufficient amounts of M cyclin
When M-Cdks become active they cause a cell to undergo mitosis. Since Cdks are kinases, what do you suppose the Cdks phosphorylate in order to initiate the different things that occur during mitosis? List two potential targets of M-Cdks.
1.) Intermediate filaments like lamin: lead to breakdown of nuclear membrane
2.) histone proteins, condensins: change packaging of DNA, so condense
3.) proteins regulating microtubules (we didn’t really talk about them in specifics, but collectively they’re called MAPs, microtubule associated proteins)
4.) other regulators of M phase, such as the kinases and phosphatases (e.g., Wee1 and Cdc25)
that regulate the activity of additional M-CDKs
The protein p53 is a tumor suppressor that is mutated in >50% of cancers. The protein product of the Ataxia-telangiectasia (AT) gene is activated following DNA damage from irradiation, and it phosphorylates p53, stabilizing p53 and increasing p53 levels in the cell. Increased levels of p53 cause the cell cycle to be paused until the DNA damage is repaired. Explain how p53 stops the cells cycle.
Phosphorylation prevents p53 from getting degraded. The active p53 can then turn on transcription of the p21 gene. The p21 gene product binds to and inhibits the Cdk complex to stop cell cycle progression.
Name the stage of M phase in which the following events occur. Place the numbers 1–8 next to the letter headings to indicate the normal order of events.
A. separation of two centrosomes and initiation of mitotic spindle assembly
B. alignment of the chromosomes at the spindle equator
C. attachment of spindle microtubules to chromosomes
D. breakdown of nuclear envelope
E. pinching of cell in two
F. re-formation of the nuclear envelope
G. condensation of the chromosomes
H. separation of sister chromatids
A. 2, prophase B. 5, metaphase C. 4, prometaphase D. 3, prometaphase E. 8, cytokinesis F. 7, telophase G. 1, prophase H. 6, anaphase
What would happen in cell division if a inhibitor of the phosphatase that removes phosphates from lamins were present?
Removal of phosphates are required for lamins to reassemble and support/form nuclear envelope. Therefore this inhibitor would prevent nuclear envelope formation which normally occurs during telophase, so likely arrested in telophase.
What would happen to cell division if inhibitors of dyneins and kinesins were present?
Would likely arrest the cell cycle in prometaphase, as the alignment of chromosomes at the metaphase plate seems to rely in part on motor proteins. Could also say Anaphase, as motor proteins help push poles apart during anaphase B.
What would happen to cell division if Latrunculin A, a drug that binds to actin monomers and prevents addition to filaments were present?
This would certainly block cytokinesis, as formation of actin filaments together with myosin needed to form contractile ring (arrest in Telophase?).
What would happen to cell division if Taxol, a drug that stabilizes microtubules (prevents depolymerization) were present?
Since lining up of chromosomes at metaphase plate requires both polymerization (partly to find chromosomes and push them to the cell center), and depolymerization (for the pull part of the push-pull mechanism), likely the cell would arrest in prometaphase.
Both colchicine (which depolymerizes microtubules) and taxol are used as cancer treatments, even though they have opposite effects on microtubules. If colchicine and taxol treatment affect all cells in the body, which of the two drugs might have the more severe side effects (outside of effects on cell division) and why?
Colchicine might have more severe effects because many cellular processes rely on intact microtubules. For example, if colchicine depolymerized microtubules in neurons, axon transport would not occur and axon transport is essential for neuron survival. It could also affect cilia.
What happens to a cell if it’s “paused” at a checkpoint but can’t be fixed?
Apoptosis
What is a MAP?
Microtubule associated protein
Where do checkpoints occur and what causes them to pause mitosis?
Beginning of G1: Damaged DNA; End of G1: Unfavorable cellular environment; End of S and beginning of G2: Damaged or incompletely replicated DNA; End of M: Chromosome improperly attached to mitotic spindle
If a cell has sustained damage that it can not repair, the cell will commit suicide through a process called programmed cell death. This process is usually called _____________ in animals.
Apoptosis
The process of programmed cell death is initiated by the activation of what?
Caspases
Caspases are proteases that can be activated by binding to cytochrome C. How is binding to cytochrome C regulated?
Cytochrome C only activates caspase when it leaks out of mitochondria
Which of the following statements are true about Bcl2 family?
- ) Some Bcl2 family members promote apoptosis, whereas others inhibit apoptosis.
- ) Some death-inhibiting members of the Bcl2 family inhibit apoptosis by blocking cytochrome c release from mitochondria.
- ) Bax and Bak are death-promoting members of the Bcl2 family that induce the release of cytochrome c from mitochondria into the cytosol.
Survival factors are important for tissues because
They increase the expression of apoptosis inhibitors so the cells won’t die.
A stem cell divides into two daughter cells and one of the daughter cells goes on to become a terminally differentiated cell. What is the typical fate of the other daughter cell?
It remains as a stem cell.
What do mitogens do?
Increase cell proliferation.
In mammals, how is therapeutic cloning different from reproductive cloning?
The cloned embryo is not implanted into a uterus, so no whole cloned organism is made.
Recently induced pluripotent stem cells have been manufactured from fibroblasts, and this approach has the potential for making stem cells from any individual that could be used for therapeutic purposes without the need for therapeutic cloning. How was this done?
Fibroblasts were transformed into stem cells by the introduction of 2-4 specific genes
In the intestine, Wnt proteins:
Promote the proliferation of the stem cells at the base of each intestinal crypt.
Would an increase in BAX levels increase chance of cell survival or death?
Increase cell death, as BAX is an apoptosis promoter (by helping form pores that allow cytochrome C into cytosol from mitochondria)
Would the release of cytochrome c into the cytosol increase chance of cell survival or death?
Increase cell death, Cytochrome C in the cytosol can activate apoptosomes, which lead to activation of caspases and apoptosis
Would overexpression of Bcl-2 lead to increase in cell survival or death?
Increase cell survival: Bcl-2 is an apoptosis inhibitor, which works through inhibiting proteins like BAX….
Would treatment of the cell with a growth factor such as NGF increase chances of cell survival or death?
Increase cell survival: NGF works as a survival factor by increasing levels of Bcl-2, which inhibits apoptosis
Would cleavage of the prodomain from procaspase increase chances of cell survival or death?
Increase cell death: removal of the pro-domain by proteolysis causes caspases to become activated, which leads to apoptosis
One form of CIPA is caused by a mutation to TrkA, one type of receptor for nerve growth factor (NGF). Explain why a nonfunctional NGF receptor might cause CIPA.
Neurons that sense pain don’t survive, since not getting signaling from survival factor NGF. So no sensory neuron for pain (separate from other senses)
CIPA can be caused by mutations to other genes as well. What might be another gene responsible for CIPA, but which is not involved in growth factor signaling?
One major example is the voltage-gated Na+ channel that is expressed only in pain sensing neurons—so can’t conduct action potential towards brain, therefore don’t sense pain even though neurons there…
What approaches cause bigger rats and which is the best one?
Overproduce mitogens (cause cell division so more cells = bigger rat) or overproduce “true” growth factors so cells get bigger but there is a limit to cell size
What would not grow larger rats but would promote cell proliferation?
Overproduce survival factors - Would have fewer cells dying during development and possibly cells would live longer rather than dying and being replaced. So might be bigger, but maybe not… Would likely have more abnormal cells that should have died so either abnormal function or more likely to get cancer or inhibit apoptosis -somewhat the same as C above, since survival factors increase expression of anti-apoptotic factors like BCL-2
What does myostatin do and, knowing this, what does the mutation do?
Inhibits muscle growth/development; mutation = abnormal muscle growth
What are the two types of cell death?
Necrosis (death by acute injury or ischemia) where cell bursts and the intracellular contents spill and inflammation response is triggered and causes oxidative damage; Apoptosis (programmed cell death) where the nucleus breaks down and cell membrane stays intact
When is apoptosis good?
Damaged or infected cells self-destruct (i.e. cancer suppression), cells infected with viruses self-destruct, regulation of lymphocyte numbers (extra cells destroyed when survival factors present), and during development it sculpts the final form (i.e. fingers and tadpole tails) and only neurons with proper connections live
When is apoptosis bad?
After stroke or any kind of ischemia causes an initial necrotic death and peripheral cells initially survive but may undergo apoptosis and aging-related oxidative damage by apoptosis
How is apoptosis initiated?
Cytochrome C released from mitochondria by 1.) membrane damage or 2.) BAX/BAK make pores in mitochondrial membrane and releases cytochrome c or cleavage of procaspase activates and causes signal cascade
How do mitogens signal for proliferation?
Mitogens activate G1 Cdk and G1/S Cdk by phosphorylation, this inactivates Rb which activates/frees transcription regulator and induces proliferation
What is an apoptosis inhibitor?
Bcl-2 that with increased levels inhibit apoptosis and promotes cancer
What are apoptosis promoters?
BAX/BAK that induces release of cytochrome c
What indicates whether a cell will die or not?
Ratio of promoters to inhibitors
How do survival factors work?
Activate transcription regulator that transcribes BCl2 gene to form BCl2 to block apoptosis
What do mitogens do?
Stimulate cell proliferation
What do growth factors do?
Stimulate cells to grow larger by stimulating intracellular signaling pathway that leads to cell growth by increased protein synthesis and decreased protein degradation
How can shape and size of organism be controlled?
Proliferation, growth, and survival vs. apoptosis
How is cell type determined?
Differential gene expression: cell communication, selective cell-cell adhesion, and cell memory
What is the difference between a malignant and benign tumor?
A malignant tumor invades and colonizes other tissues, while a benign tumor does not.
What is metastasis?
Ability of cancer cells to travel from the site of an initial tumor, through the blood or lymph to another location, and form a secondary tumor
A normal cell is converted into a cancer cell by:
An accumulation of mutations affecting several different genes.
Which of the following can increase the likelihood that a person will get cancer? (choose all the correct answers)
Living in, and adopting the lifestyles of certain countries, being obese, smoking tobacco, errors in DNA replication, which occur in all individuals over their lifetime, and infection by certain viruses, such as human papilloma virus
Which cancer-causing gene can be activated by a single mutation in only one copy?
Proto-oncogene
Which class of cancer-critical gene must be inactivated to promote the development of cancer?
Tumor suppressor gene
Which of the following properties would you expect a cancerous cell to have?
Decreased adhesion to neighboring cells
The gene that encodes p53 is
A tumor suppressor
The apoptosis promoter Bax normally found in human cells could be considered which of the following?
Tumor suppressor
A certain mutation in the receptor for epidermal growth factor (EGF) causes the mutated receptor protein to send a positive signal along associated intracellular signaling pathway even when EGF is not bound to it. This leads to abnormal cell proliferation in the absence of growth factor. On the basis of this information, how would you class the normal form of the gene for the EGF receptor?
A proto-oncogene
The Wnt pathway is normally active in precursor cells of the colon, allowing them to divide and replace absorptive intestinal epithelial cells. APC normally inhibits the Wnt pathway during differentiation into absorptive cells. What is likely to happen if APC is no longer functional in colon cells?
There will be an abnormal proliferation of precursor cells and formation of polyps.
Repetitive sequences of DNA that are found at the end of chromosomes are called
Telomeres
The enzyme that replicates the ends of linear chromosomes is called:
Telomerase
Which statement is true about human cells?
Cancer cells maintain their telomeres by reactivating the enzyme telomerase.
Some types of cancer run in families: individuals in such predisposed families are prone to develop these cancers early in adult life. Mutations in which type of cancer-critical gene would most likely be responsible for such “hereditary” cancers?
Tumor suppressor genes
Some cancer cells are missing a key protein needed to repair double-strand DNA breaks. They survive by relying on alternative DNA repair mechanisms. To treat these cancers, researchers have developed drugs that:
Inhibit alternative DNA repair mechanisms
What are the differences and similarities between a pluripotent stem cell and a precursor cell?
Similar: both cell types undergo cell division/proliferation
Different: pluripotent stems cells are capable of dividing more often than precursor cells; daughter cells from pluripotent cells can become differentiated into any cell type in the body, while daughter cells from precursor cells already have their fate determined and may become only a single or a few cell types.
Decide whether such cells exist at any time in humans and give an example.
A. Cells that do not grow and do not divide.
B. Cells that grow, but do not divide.
C. Cells that divide, but do not grow.
D. Cells that grow and divide.
A. Any terminally differentiated cells: e.g., adult neurons, red blood cells
B. Adult muscle or fat cells, neurons during development, etc.
C. Uncommon, but early in development some animals have large eggs, and a rapid cell cycle consisting of only S and M phases, so technically don’t really grow… If you say don’t exist in humans, that is OK.
D. Lots of stem cells, precursor cells, etc. throughout body
For each of the following, describe where they might come from (be specific) and different ways that they are be originally made, procured, or modified.
A. ES cell lines (normal, established)
B. ES cells from therapeutic cloning
C. iPS cells
A. Isolated from inner cell mass/blastocysts from early embryos at 16-32 cell stage (usually after in vitro fertilization), separated and grown in culture dish
B. The nucleus from an egg cell is removed and replaced with the nucleus of another, usually adult cell (possibly person who would undergo stem cell treatment), then allowed to develop to 16-32 cell stage embryo, from which the inner cell mass is removed and grown in culture.
C. Potentially any adult cell will work, but typically come from skin cells of individual (who would potentially receive treatment with stem cells). Cells are transfected with 2-4 specific genes that cause cells to de-differentiate and take on stem cell properties.
Compare the relative advantages/disadvantages of using ES cell lines, cloned ES cells and iPS
cells for medical treatments.
The disadvantages of ES cell lines compared to iPS cells are: 1) ethical issues with using human embryos—and can’t use federal funds to finance research for making ES cell lines, unless using a few existing lines, and 2) if used for therapy, ES cell lines may not match immune system of receiving individual (unless made by more difficult, not allowed therapeutic cloning procedure), while iPS cells could be made from cells from the receiving individual, so an exact match. The advantage of ES cells are that they are “natural” stem cells, while iPS cells have additional genes added to reprogram them to a stem cell state. Those additional genes may cause transplanted iPS cells, even if differentiated, to revert back to a stem cell like state and cause cancer or other abnormalities.
Why do you suppose that lung cancer deaths increased so much earlier in this century?
Most likely smoking but other things may contribute, such as diet, etc. No absolute correct answer here, but smoking seems by far the most likely…
Why do you think that the dramatic increase in lung cancer deaths in women was delayed compared to men?
Smoking became more socially acceptable for women
Why do you think might have caused the dramatic decrease in stomach cancer from 1935 to 1975?
Lots of potential answers, but likely better food safety and storage (refrigeration, preservatives, education, etc.)
What is the most common type of cancer?
Women: Breast; Men: prostate; Both: lung/bronchus
What type of cancer currently causes the most deaths in the US?
Lung
Which of the following statements about tumor suppressor genes are true?
(a) Gene amplification of a tumor suppressor gene is less dangerous than gene amplification of a proto-oncogene.
(b) Cells with one functional copy of a tumor suppressor gene will usually proliferate faster than normal cells.
(c) Inactivation of tumor suppressor genes leads to enhanced cell survival and proliferation.
(d) Individuals with only one functional copy of a tumor suppressor gene are more prone to cancer than individuals with two functional copies of a tumor suppressor gene.
A, C, and D
Which of the following genetic changes would convert a proto-oncogene into an oncogene?
(a) A mutation that introduces a stop codon immediately after the codon for the initiator methionine.
(b) A mutation within the coding sequence that makes the protein hyperactive.
(c) An amplification of the number of copies of the proto-oncogene, causing overproduction of the normal protein.
(d) A mutation in the promoter of the proto-oncogene, causing the normal protein to be transcribed and translated at an abnormally high level.
B,C, and D
For each of the following, write down if they are a proto-oncogene, an oncogene, or a tumor suppressor.
A. DNA repair enzymes
B. A constitutively active form of Ras introduced into a cell by a virus
C. Bax, an apoptosis promoter
D. PDGF
A. Tumor suppressor
B. Oncogene
C. Tumor suppressor
D. Proto-oncogene
People can inherit a mutated copy of a tumor suppressor, but don’t inherit oncogenes (mutated forms of proto-oncogenes). Why are oncogenes unlikely to come from inherited mutations?
Oncogenes are dominant genes, so affect cells. If present during development, they will affect cell division and will result in abnormal development early. If problems with development arise early, usually the embryo is miscarried, often without the woman ever realizing she was pregnant.
Human papilloma virus (HPV) is the most common sexually transmitted infection, with 45% of 20-24 yr old women infected. Infection of the genitalia and cervix with HPV increases the risk of cervical cancer 10-fold. Two proteins encoded by the HPV viral DNA bind to p53 and Rb.
A. Explain how/why the binding to ONE of those proteins would increase the likelihood of cervical cancer after HPV infection. Include in your explanation the mechanism of action.
B. For the protein you chose above, which of the following do you think would describe what that HPV protein is functionally?
A. Binding to p53 likely inhibits its function of binding to DNA as a trascription factor. p53 normally is involved in stopping the cell cycle if DNA is damaged (by turning on transcription of p21, which inhibits cdks, or apoptosis promoters) or , so if inhibited, it is more likely that the cell will divide with damaged DNA and accumulate mutations that lead to cancer.
Similar for Rb, which normally prevents transcription of genes needed for cell division by binding to promoter. If bound to HPV proteins it won’t be able to inhibit the transcription, and cell division will be more likely to occur.
B. oncogene
Carcinogenesis requires that a single cell or one of its descendants undergo a series of rare genetic and epigenetic changes that permanently alter the expression of at least five to eight genes. Thus, a common theme in things that increase cancer risk is that they cause DNA mutations. Explain why increased mutations increase cancer risk
Mutations can either cause a change in the level of the gene expressed or in the protein encoded. This can lead to conversion of proto-oncogenes to oncogenes (gain of function) by producing constitutively active mutants or by increasing the overall level of proteins produced (e.g., overproduction of growth factors). Mutations could also lead to inactivation of tumor suppressors (loss of function) either by decreasing their gene expression levels or by mutants that inactivate the proteins. Because there is some redundancy in different repair and control systems, it requires for than one tumor suppressor to be affected and more than one oncogene active to override the controls. More oncogenes present and fewer functional tumor suppressors increase the likelihood of cancer.
Your book describes these methods to treat cancer: 1) surgery; 2) induce DNA damage; 3) block new blood vessel formation (needed to feed tumor); 4) vaccinate again tumor; 5) block pathways involved in cell proliferation (e.g., Gleevec); and 6) Block mitotic spindle formation with drugs that affect microtubules. Come up with an additional potential cancer treatment (or two) without using the internet! Describe the general approach, what protein/macromolecule you might target, and why it just might work!
Here are some possible examples…
1) Block DNA synthesis – prevents cell replication
2) Inhibit cell crawling or metastasis by targeting actin cytoskeleton or adhesion proteins
3) Block cytokinesis – target myosin/actin
4) Inhibit proteases that degrade ECM – malignant cells must penetrate basal lamina from skin,
e. g.
5) Inhibit telomerase – cause cell senescence (stop dividing)
Exercise can decrease the incidence of diabetes, cancer, cardiovascular disease and neurodegeneration. It also increases autophagocytosis of mitochondria. Hypothesize why exercise- induced autophagocytosis of mitochondria might reduce aging and the risk of developing cancer.
Damaged mitochondria can produce excessive reactive oxygen species that can damage DNA, proteins and lipids, which might contribute to aging. It can also lead to leaky/damaged mitochondrial membranes and cytochrome C can leak out. Cytochrome C binding to a complex results in procaspases becoming activated and beginning caspase cascade leading to apoptosis (as caspases get activated, apoptosis is triggered). Damage to DNA can increase DNA mutations which will increase cancer risk.
What are stem cells?
Cells with the potential to become different cell types that can divide many times and produce precursor cells
What are pluripotent or multipotent cells?
Not committed to become specific cell type
What are precursor cells?
Cells able to proliferate to replace cells that divide a few times and then cell fate is determined
What is cloning?
Replace nucleus in donor egg with nucleus from individual
What is reproductive cloning?
Implant embryo and offspring are born
What is therapeutic cloning?
ES cells grown in culture and no organism is born
What is the usefulness of therapeutic cloning?
Cells match treated individual and there’s no immune response against transplanted cells
Where are sources of stem cells?
Bone marrow (hemopoietic stem cells can form all blood cell blood types), ES cells from embryo, umbilical cord cells, stem cells found in adult organisms, and transform existing cells to become stem cells
What are uses of stem cells?
Research and therapeutic uses like bone marrow replacement for leukemia patients to kill existing abnormal stem cells, then replace or grow whole organs/tissues, or replace dead neurons and muscle cells
What is cancer?
A malignant tumor
How are tumors formed?
Uncontrolled cell division
What is a malignant tumor?
Cancerous tumor that undergoes metastasis
What is metastasis?
Secondary tumor formation at other sites
How are most cancers caused?
Lifestyle/environment
How does cancer progress?
Multiple mutations happen before the cells are cancerous as there’s progressive increase in oncogenes and more tumor suppressor malfunctions
What does cancer typically require?
Presence of gain-of-function mutations in proto-oncogenes to produce oncogenes and loss-of-function tumor suppressors like p53
What does an increase in mutations lead to?
Progressively more rapid growth and tumor formation, decreased adhesion, infiltration into basal lamina, and entry into lymph and blood circulation to form secondary tumors
Where can oncogenes come from?
Virus infection and conversion of proto-oncogenes to oncogenes
What are loss of function mutations?
Lead to increased mutations and cell proliferation or cell migration
What is a DNA repair tumor suppressor?
BRCA1
What are some tumor suppressors that suppress cell cycle progression?
Bind to/inhibit cell cycle regulators (p21), turn on transcription of inhibitors (p53), or inhibit transcription (rb)
What is a tumor suppressor that turns on apoptosis?
p53, BAX
What is a tumor suppressor that inhibits growth signal pathways?
APC, NF1
What is a proto-oncogene/oncogene?
Increased proliferation or cell migration when overly active –> oncogene (dominant mutation to proto-oncogene or introduced by virus)
What are examples of proto-oncogenes and oncogenes?
Growth factors (PDGF) and receptors (EGF receptor - erbB), intracellular signaling molecules (ras), and transcription factors (myc) that turn on the production of growth factors and cyclins or reduce production of growth inhibitors
Why are you more likely to lose function if one mutated allele is inherited like BRCA1?
You have a greater likelihood of a single mutation happening somatically than two independent mutations in a cell
What are examples of environmental causes of cancer?
Skin cancer - UV (risk decreases with latitude); Oral/pharyngeal cancer - alcohol and smoking; Lung - smoking; Kidney, breast, and uterine cancer - obesity; Cervical - sexually transmitted HPV
How do carcinogens mutate DNA?
Base substitutions from molds and smoking, dimer formation from UV, and deamination (C to T) caused by free radicals/reactive oxygen species
How does asbestos increase cancer rates?
- ) Asbestos is inert, but it can’t be removed or degraded by tissues, leading to chronic inflammation
- ) Inflammation response attracts phagocytic cells which use reactive oxygen species to damage invaders
- ) This increases oxidative damage to tissues
- ) Oxidative damage to DNA causes mutations that lead to cancer
What are characteristics of aging?
Loss of skin elasticity, slowed reflexes, etc., occurs in all individuals, and affects MAX lifespan
What are characteristics of age-related diseases like cancer and neurodegenerative diseases?
Occurs only in some individuals: aging increases rate and disease affects AVG. lifespan
What are some hypotheses of aging?
Cell senescence or oxidative damage
What is cell senescence?
Normal cells in culture divide finite number of times unless telomerase becomes active
What happens after each cell division to telomeres and what happens to critically short telomeres?
Shorten; cell cycle arrest in G1
What are the effects of mitochondria damage?
Efficiency of electron transport complexes declines with age, increased generation of reactive oxygen species in damaged mitochondria with age that leads to slowed metabolism and possibly apoptosis
How do you treat cancer by killing or inhibiting dividing cells?
Prevent DNA synthesis, damage DNA to kill cancer cells lacking DNA repair via radiation, inhibit enzyme involved in DNA repair, disrupt mitosis with drugs, disrupt cytokinesis, block signaling with drugs, immunotherapy - attach toxin to antibody to target cancer cells
How can you treat cancer by blocking invasiveness?
Block proteases or target signals that regulate actin dynamics
What are other ways to treat cancer?
Inhibit angiogenesis or block vascular endothelial growth factor
What are the difficulties for preventing and treating cancer?
- ) Numerous causative factors - need different treatments for different factors
- ) Cancer treatments affect normal dividing cells like digestive tract, hair, and immune system
- ) Hard to kill slower dividing cancer stem cells
- ) Cancers evolve resistance to treatments
