Lectures 10 &11 Flashcards
What factors maintain the balance of cell number within a tissue?
Cell proliferation, cell differentiation and cell apoptosis
What are morphological steps in apoptosis?
Cell shrinkage, chromatin condensation, budding and phagocytosis
Is Bcl-2 an apoptotic factor or a survival factor?
survival factor
What role does Bcl-2 play in the process of apoptosis?
Bcl-2 inhibits the release of cytochrome C from the mitochondria
How does it accomplish this?
By binding to Bax and Bak to block pore formation in the mitochondrial membrane
What dual roles does overexpression of myc play in regulating cell number?
Stimulates both proliferation and apoptosis
How does p53 carry out its function?
Higher expression of p53 protein is induced by stress and it is a transcription factor that enhances the expression of other proteins that slow cell cycle, carry out DNA repair or induce apoptosis
What are some stresses that induce cells to elevate their p53 protein levels?
Oxidative stress, hypoxia, oncogene activation, double strand breaks
What are two methods by which tumore cells avoid apotosis?
Overexpress Bcl-2, Delete p53 gene or inactivation mutations of p53
Is p53 an oncogene or a tumor surppressor gene?
Tumor suppressor gene
What is the evidence supporting multi step process in development of cancers?
Correlation between older age and rate of cancer development Correlation between curves for smoking and lung cancer ( 35 yr offset) Polyps are seen to morph into carcinomas
Rate of colon cancer incidence lower for post-polyectomy vs. control patients
Very high rate of colon cancer In FAP patients who have high polyp numbers
What fibroblast types are the easiest to transform by oncogene transfection?
Immoratilzed mouse and rat cells (e.g. 3T3 or Rat-1 cells)
How many oncogenes are required?
one
How many oncogenes are required to transform primary mouse and rat fibroblasts?
Two
Can human fibroblasts be transformed with myc+ ras transfection?
No
Can myc+ ras transform immortalized (with telomerase + large T antigen) human fibroblasts?
Yes, as measured by in vitro assays but cells do not form tumors in nude mice
What is a telomere?
A multiply repeated sequence of DNA at the ends of each chromosome
How do telomeres function as count down clocks for number of cell divisons?
They shorten with each division and cells die when telomeres become too short
How can you immortalize human fibroblasts or epithelial cells?
Insert gene for telomerase into cells
What are the 6 traits required for a full blown metastatic tumor?
Self sufficiency in growth signals
Insensitivity to anti growth signals
Evasion of apoptosis
Limitless replication potential
Sustained angiogensis
Tissue invasion and metastasis
How can the tumor cell achieve self sufficiency?
Manufacture is own GF , overexpress receptors , activated signaling protein downstream from receptor
How man tumor insensitivity to anti growth signals?
Delete or inactivate Rb, delete p15^INK4B, infect with HPV
How can a tumor evade apoptosis?
Overexpress Bcl-2, delete or inactivate p53, overexpress MDM2
How can a tumor achieve limitless replication?
Re express telomerase, overexpress myc
How can a tumor achieve sustained angiogenesis?
Turn on expression of VEGF or PDGF
How can a tumor achieve tissue invasion and metastasis?
Overexpress RhoC or turn back on expression of Twist
