Cell Cycle Control and Cancefr Flashcards
What happens in normal cell division if there is a problem that isn’t fixed?
apoptosis (cell suicide pathway)
what happens in unregulated cell division if there is a problem that isn’t fixed?
it goes through checkpoint anyways
what is signal transduction?
external signal -> internal response
- reception, transduction, activation of cellular response
- signal/growth factor binds to its receptor
what are the properties of normal cells?
- anchorage dependence
- contact inhibition (density-dependent, a natural process where cell growth and movement stop when cells come into contact with each other, forming a monolayer)
what’s the difference between benign and malignant tumors?
benign: noncancer
malignant: cancerous
what is metastasis?
when cancer spreads from original tumor
what are proto-oncogenes?
genes that encode signals, receptors, signaling molecules, and control proteins
what are oncogenes?
mutated or overactive versions of proto-oncogenes through point mutation, gene amplification, or translocation (transduction pathways always stimulated -> increased cell division)
what do tumor suppressor proteins do?
inhibit cell division
what if a tumor suppressor protein is mutated?
cell cycle checkpoints are ignored and damaged cells proliferate
what happens if ABL fuses with BCR?
ABL (proto-oncogene) fuses with BCR, is not expressed correctly -> cells over-proliferate -> leukemia
what happens with a BRCA mutation?
BRCA mutation -> damaged DNA still goes through mitosis -> increased risk for breast and ovarian cancer
what happens if p53 is mutated?
p53 mutation -> damaged DNA/cells go through mitosis
- p53 is the “master watchman” for preventing cancer
how can tumor suppressor genes be silenced?
- abnormal methylation (epigenetic)
hyper-methylated -> gene off -> no tumor suppressor made
what happened to mice who were engineered to make telomerase in all their cells?
cancer
what does RNAi (RNA inhibition) do for cancer?
gets rid of telomerase in cancer cells
what is traditional chemotherapy?
- injection of chemicals into bloodstream to kill dividing cells
- non-selective
- Taxol: prevents kinetochore microtubules from shortening
what is radiation therapy?
high energy
particles damage DNA more in cancer cells that normal cells-> cells destroyed/injured and can’t repair damage
localized
where are the cell cycle control checkpoints?
G1, G2, Mitosis (by signaling molecules present in the cytoplasm)
what is the most important checkpoint?
G1
what happens during G1 checkpoint?
- is cell division necessary?
- does it have enough growth factors?
what happens during G2 checkpoint?
- was DNA replicated correctly?
- Is the cell large enough?
what happens during M checkpoint?
- are all the chromosomes attached to microtubules?
what happens if “no” at a checkpoint?
halted, cell may die
what are the regulatory molecules?
protein kinases and cyclins
what are protein kinases?
enzymes that activate or inactivate other proteins by phosphorylating them. to be active, must be attached to cyclin (cyclin-dependent kinases / cdks)
what is cyclin?
a protein with cyclically fluctuating concentration in cell
what is mpf?
- maturation/m-phase promoting factor
- cyclin + cdk
- acts as a kinase and activates other kinases
contributes to molecular events required for chromosome condensation and spindle formation in prophase
what is G0 phase?
nondividing state
what is growth factor?
- a protein released by certain cells that stimulates other cells to divide
what is density-dependent inhibition?
cells are crowded so they stop dividing
what is anchorage dependence?
to divide, animal cells must be attached to something
why are cancer cells “immortal”
- don’t stop dividing when growth factors are depleted
- don’t heed normal signals that regulate cell cycle
- don’t listen to controls that trigger cells to undergo apoptosis when something’s wrong
- if they stop dividing, it’s at random points
what have cells gone through that can dividing indefinitely?
transformation
how can a tumor be formed?
- if a cancer cell evades destruction by body that can tell the cell is “nonself”, it may proliferate
what is a tumor?
a mass of abnormal cells within otherwise normal tissue
how does a malignant tumor spread?
1) tumor grows from single cancer cell
2) cancer cells invade neighboring tissue
3) cancer cells spread through lymph and blood vessels to other parts of body
4) a small % of cancer cells may mestastasize to another part of the body
what can happen to tumor cells?
may have unusual # of chromosomes, metabolism may be altered, may cease to function in constructive way
how can oncogenes result from epigenetic change?
mutation in a gene for a chromatin-modifying enzyme can lead to loosening of chromatin and inappropriate expression of proto-oncogene
how can oncogene result from translocation?
gene moved to new locus, under new controls
how can oncogene result from gene amplification?
multiple copies of the gene
how can oncogene result from point mutations?
within a control element or within the gene
what are tumor suppressor genes?
inhibit cell division
if mutated -> cancer
their protein products repair DNA, control adhesion to cells
what is ras proto-oncogene? (encoded by ras gene)
G protein that relays a signal from a growth factor receptor on plasma membrane to protein kinases
what if a ras gene is mutated?
production of hyperactive ras protein that triggers kinase cascade even without growth factor
what is the p53 protein?
transcription factor that promotes synthesis of cell cycle, inhibiting proteins.
what if p53 protein is mutated?
excessive cell growth
what is p53 gene?
“guardian angel of the genome”bc it prevents cell from passing on mutations due to DNA damage
how is cancer development multistep?
- more than one mutation or epigenetic change generally needed
- mutation usually must knockout both tumor-suppresor alleles (recessive) to block tumor suppression
what are tumor viruses?
Epstein-Barr virus, HPV, HTLV-1
- viruses can interfere with gene regulation in several ways if they integrate their genetic material into DNA of cell
