Neoplasia V

Question 1

What is the function of the APC gene, and what are the cancers associated with it?

Answer 1

Function = prevents nuclear transcription by binding to Beta-catenin

CA= familial polyposis coli

Question 2

What is the function of the BRCA-1/2 genes, and what are the cancers associated with it?

Answer 2

Function = Regulates DNA repair

CA= breast/ovarian CA

Question 3

What is the function of the Rb gene, and what are the two cancers associated with it?

Answer 3

Inhibits G1 to S phase

Retinoblastoma
Osteogenic sarcoma

Question 4

What is the function of the TGF-beta gene, and what are the cancers associated with it?

Answer 4

Inhibits G1 to S phase

Pancreatic and colorectal gene

Question 5

What is the function of the WT-1/WT-2 gene, and what are the cancers associated with it?

Answer 5

Regulates nuclear transcription

Wilms tumor
Beck-wiedemann syndrome

Question 6

What is the WNT signalling pathway?

Answer 6

Controls cell fate, adhesion, and polariry during embryonic development

Question 7

the APC gene and beta-catenin gene are involved in what pathway?

Answer 7

WNT

Question 8

What is the function of APC protein in the WNT pathway?

Answer 8

Down regulates Beta-catenin to prevent its accumulation

Question 9

What happens in the WNT pathway when WNT binds?

Answer 9

Inactivation of the APC, leading to increase beta-catenin levels

Question 10

What does beta-catenin bind to?

Answer 10

TCF factor in the DNA

Question 11

What type of CA does beta-catenin upregulation lead to?

Answer 11

FAP

Question 12

What are the three CAs that are associated with the Rb gene?

Answer 12

Retinoblastoma
Osteosarcoma
Soft tissue sarcoma

Question 13

What percent of Rb dysfunctions are familial? Sporadic?

Answer 13

60% sporadic

40% familial

Question 14

What is Knudson’s two hit hypothesis?

Answer 14

Both alleles of Rb must be inactivated/mutated for CA to develop

Question 15

Where does the “second hit” occur in familial Retinoblastoma?

Answer 15

Retinal cells (first in somatic cells)

Question 16

True or false: Heterozygous Rb genes form CA

Answer 16

False–need homozygous

Question 17

What is the function of the p53 gene? Associated CAs?

Answer 17

function = inhibits G1 to S phase, repairs DNA, activates BAX

Lung, colon, breast CA

Question 18

What is Li-Fraumeni syndrome?

Answer 18

CA caused by inactivation of p53

Question 19

What is the specific pro-apoptotic protein that p53 activates?

Answer 19

BAX

Question 20

p53 arrests the cell cycle at which phase? How?

Answer 20

G1/S phase

Acts via p21 (cyclin CDK4 inhibition)

Question 21

What is the function of p21?

Answer 21

G1 arrest (cyclin CDK4 inhibition)

Question 22

What is the function of GADD45 that p53 upregulates?

Answer 22

DNA repair mechanism

Question 23

What happens to p53 in tumors?

Answer 23

Inactivated (mutated)

Question 24

What is the function of HPV E6 protein?

Answer 24

inhibits p53

Question 25

What is the function of HPV E7 protein?

Answer 25

inhibit p21 and Rb-E2F

Question 26

What is the function of VHL? What chromosome is it one?

Answer 26

Anti tumor gene on chr 3. Part of the ubiquitin ligase complex that regulates the HIF-1alpha transcription

Question 27

What are the CAs associated with VHL mutations?

Answer 27

Hereditary renal cells carcinomas Pheochromocytomas Hemangioblastomas of CNS

Question 28

What is Warburg effect?

Answer 28

Even in presence of ample O2, CA cells demonstrate a distinct form of metabolism characterized by high levels of glucose uptake and increased concentration of glucose to lactose via the **glycolytic pathway**

Question 29

What is the basis for PET scans?

Answer 29

Tumors like Glucose (Warburg effect) Thus can label glucose

Question 30

True or false: Carcinogenesis occurs in a single step

Answer 30

False--multistep process and accumulation of mutations

Question 31

How long does telomerase last in normal cells? Then what happens (normally)?

Answer 31

60-70 doublings, then p53 activated

Question 32

What is the function of telomerase in CA development?

Answer 32

Maintains telomere length

Question 33

DNA methylation upregulates or downregulate gene expression? How?

Answer 33

Downregulates-- condenses chromosome

Question 34

What are miRNAs?

Answer 34

family of 19-24 nucleotides that regulate mRNA function at the posttranscriptional level

Question 35

What percent of cancer are the result of chemical carcinogens?

Answer 35

80-90%

Question 36

What are chemical carcinogens?

Answer 36

highly reactive electrophiles that remove electron from DNA

Question 37

What does it mean when a carcinogen has a "direct action" effect?

Answer 37

Act without modification

Question 38

What does it mean when a carcinogen has an "indirect action" effect?

Answer 38

Require metabolic activation

Question 39

What is the relationship between promoters and initiators?

Answer 39

Promoter given **after** initiator, and in a short time frame, is associated with CA development

Question 40

What are initiators

Answer 40

Chemical that initiate carcinogenesis, and produce cell alteration Not sufficient for tumor formation

Question 41

What are promoters?

Answer 41

Induces tumors in initiated cells Non-tumorigenic by themselves

Question 42

What are polycyclic aromatic hydrocarbons?

Answer 42

Products of combustion | Associated with lung and bladder CAs

Question 43

What type of CAs are associated with aromatic amines and Azo dyes? MOA?

Answer 43

liver CA action of p450 cytochrome oxygenase system

Question 44

What is beta-naphthylamine? What CA is it associated with?

Answer 44

Material used in rubber industry Bladder CA

Question 45

What is Aflatoxin B1?

Answer 45

Carcinogenic mycotoxin produced by aspergillus flavus in corn/peanuts

Question 46

What is the effect of Aflatoxin B1?

Answer 46

Hepatocellular carcinoma d/t p53 mutation

Question 47

What is the MOA of Nitrosamines and amines

Answer 47

Formed in Gut of humans, associated with gastric carcinoma

Question 48

Asbestos is associated with what CAs?

Answer 48

Mesothelioma (but lung CA more often)

Question 49

Chromium, nickel associated with what CAs?

Answer 49

lung CA

Question 50

Arsenic is associated with what type of CA?

Answer 50

Skin CA

Question 51

What is the effect of estrogen in carcinogenesis? What CA is this associated with?

Answer 51

Promoter of chemical carcinogenesis Liver CA

Question 52

What is the effect of diethyl-stilbesterol?

Answer 52

Promoter of Postmenopausal endometrial CA

Question 53

What is the MOA of high fat diet?

Answer 53

Increased bile acid production Colon CAs

Question 54

What are the molecules associated in the WNT pathway, and how do they lead to CA?

Answer 54

WNT receptor inhibits APC from inhibiting Beta catenin. If there is no APC d/t mutation, then FAP

Question 55

p53 acts through what other p# molecule to inhibit CDK4/cyclin

Answer 55

P21

Question 56

What is the MOA of direct carcinogens? Indirect?

Answer 56

``` Direct = React with DNA Indirect = usually metabolized by p450 ```