Lecture 31

Question 1

6 important hallmarks of cancer

Answer 1

1. sustaining proliferative signaling
2. evading growth suppressors
3. activating invasion and metastasis
4. replicative immortality
5. angiogenesis
6. resisting cell death

Question 2

describe normal vs transformed 3T3 cells

Answer 2

normally stop growing when confluent bc of contact inhibition

with Src oncogene, no contact inhibition so will keep growing

Question 3

what 2 hallmarks of cancer are involved in transformed 3T3 cells?

Answer 3

1. sustaining proliferative signals
2. evading growth inhibition

Question 4

example of cancer that is genetic disease

Answer 4

Li-Fraumeni syndrome

Question 5

genes involved in breast and ovarian cancer

Answer 5

BRCA1, BRCA2

Question 6

gene involved in Li-Fraumeni syndrome

Answer 6

p53

Question 7

gene involved in familial adenomatous polyposis (colorectal cancer)

Answer 7

APC

Question 8

gene involved in retinoblastoma

Answer 8

RB1

Question 9

what are oncogenes?

Answer 9

activated to drive tumorigenesis (positive regulators)

Question 10

what are tumour suppressors?

Answer 10

inactivated to drive tumorigenesis (negative regulators)

Question 11

describe involvement of DNA repair genes in cancer

Answer 11

prevent mutations to maintain DNA integrity

Question 12

describe discovery of RSV

Answer 12

1. crush up sarcoma from chicken
2. pass filtrate thru fine-pore filter that does not block viruses
3. inject filtrate into chicken
4. chicken develops sarcoma

therefore, RSV carrying cancer-causing gene

Question 13

what is the cancer-causing gene in RSV?

Answer 13

v-Src

Question 14

what kind of gene is v-Src?

Answer 14

oncogene

Question 15

what is c-Src?

Answer 15

the proto-oncogene

Question 16

what is a proto-oncogene?

Answer 16

required for normal cell function but when mutated become oncogene

Question 17

how do retroviruses make oncogenes? (5 steps)

Answer 17

1. virus infects and creates provirus next to proto-oncogene
2. cell transcribes provirus and proto-oncogene
3. when virus reproduces, proto-oncogene is incorporated into virus
4. with repeated rounds of viral infection and replication, proto-oncogene becomes rearranged/mutation (this is when it becomes a problem!)
5. now oncogene is inserted back in host chromosome and promotes cancer

Question 18

alternative way how retroviruses make oncogenes

Answer 18

1. virus infects and creates provirus next to proto-oncogene
2. strong viral promoter stimulates overexpression of proto-oncogene

Question 19

are all proto-oncogenes activated from viruses?

Answer 19

no

Question 20

2 ways (other than viruses) that proto-oncogenes are activated?

Answer 20

1. mutations in coding sequences
2. chromosome abnormalities

Question 21

2 chromosome abnormalities that lead to proto-oncogene activations?

Answer 21

1. increased expression
2. fusion protein

Question 22

what is RTK?

Answer 22

cell surface protein that binds extracellular signaling molecules, leading to phosphorylation of tyrosine residues

Question 23

describe how RTK activates Ras

Answer 23

1. growth factor binds RTK
2. adaptor molecules bind the receptor, linking RTK to Ras
3. Ras binds GTP and is activated
4. GTP-Ras binds Raf to cause phosphorylation cascade
5. activates TFs that promote cellular growth

Question 24

what kind of protein is Ras?

Answer 24

GTPase

Question 25

what kind of protein is Raf?

Answer 25

kinase

Question 26

describe normal regulation of Ras

Answer 26

normally has intrinsic GTPase activity so GTP-Ras automatically turns into GDP-Ras

Question 27

why is it important that GTP-Ras can automatically become GDP-Ras?

Answer 27

so it's not constitutively on and activating genes for cell growth

Question 28

what causes Ras to become dysregulated and drive tumorigenesis?

Answer 28

1 point mutation in AA 12 turns Ras from proto-oncogene to oncogene

Question 29

describe oncogene form of Ras

Answer 29

stuck in GTP-Ras state so it is constitutively on

Question 30

are oncogene mutations haplosufficient or haploinsufficient? why?

Answer 30

haploinsufficient because oncogene mutations are DOMINANT

Question 31

describe oncogene mutants as dominant

Answer 31

mutants creating oncogenes are DOMINANT --> 1 copy of mutant allele is enough to induce excessive cell proliferation

Question 32

difference btwn cancer mutation and mendelian genetic diseases

Answer 32

cancer involves mutation in single cell to make disease other genetic diseases inherited by mendelian genetics affect every cell in an organism

Question 33

what causes Burkitt lymphoma?

Answer 33

reciprocal translocation btwn Chr 8 and Chr 14 in B cells

Question 34

what gene is involved in Burkitt lymphoma?

Answer 34

c-Myc

Question 35

what is c-Myc?

Answer 35

TF whose normal function promotes cellular growth/proliferation (proto-oncogene)

Question 36

what chromosome is Myc on?

Answer 36

chromosome 8

Question 37

describe how translocation leads to activation of c-Myc into oncogene

Answer 37

regulatory element of chromosome 14 is for immunoglobulin when translocation, this regulatory element is upstream of Myc and leads to overexpression of Myc --> Myc loses tight regulation

Question 38

what causes chronic myelogenous leukemia?

Answer 38

translocation btwn chromosome 9 and 22

Question 39

what is c-Abl?

Answer 39

protein kinase involved in cell survival

Question 40

what is produced in the CML translocation?

Answer 40

Bcr1-Abl chimeric protein is made and is a HYPERACTIVATED KINASE

Question 41

why is it easy to target Bcr-Abl?

Answer 41

bc not found in normal cells