Lectures 7 and 8: Cell Birth and Death I and II - Basic Flashcards
Types of reversible altered proliferative states
Regeneration, hyperplasia, metaplasia, dysplasia
Regeneration
One for one replacement of an existing cell that has died with a fully differentiated cell of the same type (always physiologically helpful)
Hyperplasia
Over-growth or an increase in the number of cells in a tissue, all cells are fully differentiated and functional (straddles healthy v. pathologic)
Metaplasia
Replacement of cells of one cell type for those of another cell type; adaptive substitution (always physiologically harmful)
Dysplasia
Cells are losing proliferation and positional control, nuclei of these cells are larger than normal cells around it, cells appear different in size and shape from surrounding cells of the same type (pleiotropy), these cells are often precancerous
Neoplasia
Irreversible proliferation of cells; proliferation continues in the absence of an external stimulus
True or false: Neoplasia is synonymous with tumor.
True
True or false: Neoplasia is synonymous with cancer.
False
Benign tumor
Cells have only lost proliferation controls
Where does regeneration occur?
In the liver and endothelium
True or false: A benign tumor can kill a patient.
True
What does it mean to be a “blood compatible” surface and where is this seen in the body?
Blood cells will not stick to this type of surface - it is found in endothelial tissue lining the lumen of blood vessels.
What is a risk of hyperplasia of smooth muscle following a balloon angioplasty?
If there is too much smooth muscle cell proliferation, then it could accumulate inside the artery and restrict the amount of blood flow through the vessel. This would result in an increased blood pressure.
What is Grave’s disease an example of and what is another name for this condition?
Hyperplasia; it is also called hyperthyroidism
Malignant tumor
Cells have lost proliferation and positional controls
What are some symptoms of Grave’s disease?
Bulging eyes, strabismus, over production of thyroid hormone as there is an increase in the number of fully functional thyroid cells
What is an example of hyperplasia that is helpful?
Erythrocyte hyperplasia in bone marrow following blood loss or changes in altitude (low to high)
What is an example of metaplasia? Is it helpful or harmful?
The replacement of ciliated columnar epithelial cells in the endocervix with several layers of squamous epithelial cells during chronic pelvic inflammatory disease (CPID). This is harmful.
Where else do you see metaplasia and what causes it?
It can occur in the respiratory tract of smokers. Similarly to CPID, ciliated columnar epithelial cells are replaced with squamous epithelial cells.
What are two key examples of dysplasia?
Cervical dysplasia as seen on abnormal Pap smears; dysplastic moles (nevi) removed from the skin
Uterine fibroids
Benign neoplasia of smooth muscle cells
True or false: The position of a cell within a tissue can determine its rate of proliferation.
True
True or false: Information in the ECM has nothing to do with the regulation of cell proliferation.
False
What are symptoms of uterine fibroids?
Abnormal and heavy bleeding, pain and pressure, fertility problems
What is an example of positional control of proliferation?
Intestinal crypt cells
What are the four major stages of the cell cycle?
G1, S, G2, M
G1
Gap 1 - Prepares cells for replicating DNA; cell is busy doubling its contents in preparation of a cell division
S
Synthesis - DNA replication
G2
Gap 2 - Prepares cell for segregation/division of genome and cytoplasm
M
Mitosis - Chromosome segregation (mitosis) and separation of daughter cells (cytokinesis)
When are checkpoints imposed in the cell cycle?
G1, S, G2, and M
What genetic issues are screened for at the cell cycle checkpoints?
DNA damage, completeness of DNA replication, alignment of chromosomes
What other things are looked for at checkpoints?
Availability of sufficient key nutrients and cytokines in the environment
R-point
The point, during G1, at which cells make the decision to continue through the cell cycle or to exit the cycle and enter a quiescent state, called G0 based on
What is the Cyclin-Cdk pair for the G1 phase?
Cyclin D with Cdk4 or Ckd6
What is the Cyclin-Cdk pair for the G1/S phase?
Cyclin E with Cdk 2
What is the Cyclin-Cdk pair for the S phase?
Cyclin A with Cdk 2
What is the Cyclin-Cdk pair for the M phase?
Cyclin B with Cdk1
True or false: The R-point is defective in cancer cells.
True
Damaged DNA induces expression of what protein?
p53
What happens when p53 builds up in the cell?
It signals the cell to undergo apoptosis
What is an important regulator of the S-phase?
Cyclin A
What is a key regulator in mitosis?
Cyclin B or M-cyclin
How do cyclins work?
They bind cyclin-dependent kinases (Cdk’s)
What are key substrates for Cyclin B-cdk1 complexes?
lamins (nuclear disassembly) and histones (more compact when they’re phosphorylated)
What types of kinases work on M-Cdk and in what order?
First, an inhibitory kinase phosphorylates it, then an activating kinase phosphorylates it
When and how is the M-Cdk activated?
An activating phosphatase removes the inhibiting phosphate
What does Rb protein do?
It regulates cell cycle transit, particularly through the R-point
What will result from mutated Rb protein?
A tumor
When is Rb protein active?
When it’s under- or dephosphorylated
What does active Rb protein do?
It binds certain transcription factors and prevents them from binding and transcribing DNA
What does a mitogen do and what is the result of the signaling pathway that it induces?
It induces or stimulates mitosis by activating a signaling pathway that increases the synthesis of cyclin D and cdk’s 2, 4, and 6, and then the synthesis of cyclin E increases
True or false: Cyclin D is promiscuous.
True
What do cyclins D and E with their cdk partners do?
They phosphorylate Rb protein
What is the result of phosphorylated Rb protein?
This causes the protein to be inactive and unable to bind transcription factors, so DNA will be transcribed and the cell will proliferate
What do oncogenes encode?
Mutated signaling proteins
What is another name for the cyclin B-cdk1 complex?
MPF
Which phosphate is always dominant in terms of the phosphorylation of M-cdk?
The inhibitory phosphate
What is an important factor besides mutated signaling proteins in developing cancer?
The tissue environment of a cell
How common are oncogenes?
Almost every known tumor has at least one oncogene
Which of these is irreversible? Which are reversible? What are they in order of increasing severity? Which of these can be good?* neoplasia* regeneration* metaplasia* hyperplasia* dysplasia
Reversible: Regeneration (good)
Which altered proliferative state corresponds tothe following condition/disease?liver transplanta) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
liver transplant - regeneration (1 for 1) (good)Regeneration: 1-for-1 replacement of lost cells by the same cell type
Which altered proliferative state corresponds tothe following condition/disease?vascular surgery (for arteriostenosis)a) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
vascular surgery for arteriostenosis (regeneration) (1 for 1) (good)Regeneration: 1-for-1 replacement of lost cells by the same cell type
Which altered proliferative state corresponds tothe following condition/disease?adapting to high altitude or blood lossa) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
adapting to high altitude or recovering from blood loss: hyperplasia of RBC (hyperplasia) (good)Hyperplasia: increase in the number of cells in a tissue; cells are fully differentiated. Can be physiological (helpful) or pathological (harmful).
Which altered proliferative state corresponds tothe following condition/disease?restenosis after balloon angioplasty (post-atherosclerosis)a) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
restenosis after atherosclerosis surgery - hyperplasia (bad)Hyperplasia: increase in the number of cells in a tissue; cells are fully differentiated. Can be physiological (helpful) or pathological (harmful).
- Which altered proliferative state corresponds tothe following condition/disease?Grave’s diseasea) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia2. What is Grave’s disease?
Grave’s disease - hyperplasia - badHyperplasia: increase in the number of cells in a tissue; cells are fully differentiated. Can be physiological (helpful) or pathological (harmful).* hyperthyroidism* hyperproliferation of thyroid cells
Which altered proliferative state corresponds tothe following condition/disease?chronic smokers: ciliated columnar cells are replaced by stratified squamous cells, which is more protective ofthe tissue but also includes mucus issuesa) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
smokers: ciliated columnar cells replaced by stratified squamous cells - metaplasia - badmetaplasia: adaptive substitution of one cell type for another
What is hypertrophy?
Hypertrophy (not covered in class!/not on the exam!)An increase in the size or volume of a cell. Not an altered proliferative state. Examples include muscle cells of a bodybuilder, adipose cells during fat accumulation, oocytes during maturation.
What are the 4 altered states of proliferation that are reversible? What does “reversible” mean?
Altered proliferative states of cells that are reversible: proliferation stops when the stimulus that provoked it is removed.Regeneration, Hyperplasia, Metaplasia and Dysplasia
What is neoplasia? Is it reversible/irreversible? Is it good/bad?
Irreversible proliferation: proliferation continues in the absence of an external stimulus. (bad) (benign or metastatic tumor growth)
Which altered proliferative state corresponds tothe following condition/disease?abnormal Pap Smear in womena) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
cervical dysplasia - dysplasia - badDysplasia: activated metabolic pathways for proliferation; loss of orientation in a tissue. Abnormal appearance (pleiotropy, disorientation within tissue, high mitotic rate) of cells.Dysplasia is often a precursor to cancer, thus the need for careful monitoring or prophylactic surgery when it is detected.
Which altered proliferative state corresponds tothe following condition/disease?abnormal moles removed from skina) regenerationb) hyperplasiac) metaplasiad) dysplasiae) neoplasia
dysplastic moles removed from skin - dysplasia - badDysplasia: activated metabolic pathways for proliferation; loss of orientation in a tissue. Abnormal appearance (pleiotropy, disorientation within tissue, high mitotic rate) of cells. Dysplasia is often a precursor to cancer, thus the need for careful monitoring or prophylactic surgery when it is detected.
- Which CDKs/cyclins are necessary for a cell to move through the R point?2. What stages of the cell cycle does the R point mediate?
G1 –> R point2 fates–> G0 (if not enough nutrients/factors/quiescent, 99.99% cells)or–> G1* needs Cyclin D (CDK 4/6) and Cyclin E (CDK 2) to move from G1 through the R point to S
Describethe steps that the CDKs/cyclins go through at the M checkpoint of the cell cycle.
- Mitotic CDK (CDK1) + M-cyclin (Cyclin B) –>CDK1-CyclinB (MPF = mitosis promoting factor)2.CDK1-CyclinB (MPF = mitosis promoting factor) + inhibiting kinase –> CDK1-CyclinB-Pinh3. CDK1-CyclinB-Pinh + activating kinase –> CDK1-CyclinB-Pinh, PactPinh»_space;Pact4. activating phosphataseremovesPinh5.CDK1-CyclinB-Pact = ON* without MPF kinase activity: phosphatases dephosphorylate lamins, histones, nucleolins –> decondensation of chromosomes, reassembly of nuclear envelope and nucleolus* with MPF kinase activity: Phosphorylation of lamins, histones –> chromosomes condense –> mitosis
Describe the steps that CDKs/cyclins go through to pass through the R point of the cell cycle
