Lectures 10 &11

Question 1

What factors maintain the balance of cell number within a tissue?

Answer 1

Cell proliferation, cell differentiation and cell apoptosis

Question 2

What are morphological steps in apoptosis?

Answer 2

Cell shrinkage, chromatin condensation, budding and phagocytosis

Question 3

Is Bcl-2 an apoptotic factor or a survival factor?

Answer 3

survival factor

Question 4

What role does Bcl-2 play in the process of apoptosis?

Answer 4

Bcl-2 inhibits the release of cytochrome C from the mitochondria

Question 5

How does it accomplish this?

Answer 5

By binding to Bax and Bak to block pore formation in the mitochondrial membrane

Question 6

What dual roles does overexpression of myc play in regulating cell number?

Answer 6

Stimulates both proliferation and apoptosis

Question 7

How does p53 carry out its function?

Answer 7

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

Question 8

What are some stresses that induce cells to elevate their p53 protein levels?

Answer 8

Oxidative stress, hypoxia, oncogene activation, double strand breaks

Question 9

What are two methods by which tumore cells avoid apotosis?

Answer 9

Overexpress Bcl-2, Delete p53 gene or inactivation mutations of p53

Question 10

Is p53 an oncogene or a tumor surppressor gene?

Answer 10

Tumor suppressor gene

Question 11

What is the evidence supporting multi step process in development of cancers?

Answer 11

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

Question 12

What fibroblast types are the easiest to transform by oncogene transfection?

Answer 12

Immoratilzed mouse and rat cells (e.g. 3T3 or Rat-1 cells)

Question 13

How many oncogenes are required?

Answer 13

one

Question 14

How many oncogenes are required to transform primary mouse and rat fibroblasts?

Answer 14

Two

Question 15

Can human fibroblasts be transformed with myc+ ras transfection?

Answer 15

No

Question 16

Can myc+ ras transform immortalized (with telomerase + large T antigen) human fibroblasts?

Answer 16

Yes, as measured by in vitro assays but cells do not form tumors in nude mice

Question 17

What is a telomere?

Answer 17

A multiply repeated sequence of DNA at the ends of each chromosome

Question 18

How do telomeres function as count down clocks for number of cell divisons?

Answer 18

They shorten with each division and cells die when telomeres become too short

Question 19

How can you immortalize human fibroblasts or epithelial cells?

Answer 19

Insert gene for telomerase into cells

Question 20

What are the 6 traits required for a full blown metastatic tumor?

Answer 20

Self sufficiency in growth signals
Insensitivity to anti growth signals
Evasion of apoptosis
Limitless replication potential
Sustained angiogensis
Tissue invasion and metastasis

Question 21

How can the tumor cell achieve self sufficiency?

Answer 21

Manufacture is own GF , overexpress receptors , activated signaling protein downstream from receptor

Question 22

How man tumor insensitivity to anti growth signals?

Answer 22

Delete or inactivate Rb, delete p15^INK4B, infect with HPV

Question 23

How can a tumor evade apoptosis?

Answer 23

Overexpress Bcl-2, delete or inactivate p53, overexpress MDM2

Question 24

How can a tumor achieve limitless replication?

Answer 24

Re express telomerase, overexpress myc

Question 25

How can a tumor achieve sustained angiogenesis?

Answer 25

Turn on expression of VEGF or PDGF

Question 26

How can a tumor achieve tissue invasion and metastasis?

Answer 26

Overexpress RhoC or turn back on expression of Twist