Lecture 12 - Cancer

Question 1

Cellular characteristics associated with human cancers

Answer 1

Increased number of growth factor receptors
RAS protein activated by mutations
Abl kinase activated by abnormal chromosomes in CML
Src kinase activated by mutations
Mutated or deleted pRB
Mutated or deleted p53

Question 2

Retinoblastoma

Answer 2

Rare tumor that arise from neural precursor cells in the immature retina.

Question 3

True or false: A large number of mutations are necessary for a retinoblastoma develop.

Answer 3

False

Question 4

How many forms of retinoblastoma are there and what are they?

Answer 4

There are two forms, one is hereditary and the other is not

Question 5

True or false: The Rb gene is frequently missing in several other types of cancer

Answer 5

True

Question 6

What is bound to RAS when it’s in the “on” position? What is bound to in in the “off” position

Answer 6

GTP = on
GDP = off

Question 7

What converts RAS from the on to the off and vice versa?

Answer 7

GTPas activating proteins (GAPs)

Question 8

What does the NF1 gene encode and what is its significance as it relate to cancer?

Answer 8

It encodes neurofibromin which includes a GAP domain and is associated with café-au-lait spots and benign neurofibromas; defective signal transduction possibly through RAS

Question 9

What are fos and jun?

Answer 9

transcription factors

Question 10

True or false: Tumor cells often have overexpression of fos and jun.

Answer 10

True

Question 11

What is up-regulated in Burkitt’s lymphoma and what causes it?

Answer 11

Myc is up-regulated because of a translocation that moves the myc gene against a promotor for IgH chains that are constitutively expressed

Question 12

True or false: Chromosome translocations are associated with leukemias and lymphomas.

Answer 12

True

Question 13

What do viral proteins made by cancer-causing viruses sequester? What does this lead to?

Answer 13

p53 and pRB

unregulated cell proliferation

Question 14

What does HPV target?

Answer 14

p53 and pRB

Question 15

Which HPV genes target which proteins?

Answer 15

E6 binds and induces proteolysis in p53

E7 binds and inactivates pRB

Question 16

What are the 6 hallmarks of cancer?

Answer 16

1. Evading apoptosis (p53 problem)
2. Self-sufficiency in growth signals (RAS mutation, always turned on, bound to GTP)
3. Insensitivity to anti-growth signals (pRB mutation)
4. Sustained angiogenesis (blood vessel genesis)
5. Limitless replicative potential (all tumors will have turned on telomerase, mitotic clock is gone; up-regulation of telomerase
6. Tissue invasion and metastasis

Question 17

True or false: Familial adenomatous polyposis coli is caused by the accumulation of mutations in colon cells over time.

Answer 17

True

Question 18

True or false: Genetic stability is associated with cancer.

Answer 18

False