cancer continued

Question 1

Factors that affect cancer

Answer 1

Genetic and environmental

Question 2

Genetic factors example

Answer 2

-BRCA mutation
-BRCA is a tumour suppressor mutation and both BRCA1 and BRCA2 cause a 5x chance of developing breast cancer in woman and 10-30x chance of developing ovarian cancer

Question 3

Environmental factors example

Answer 3

The frequency of Burkitt’s lymphoma is much higher in individuals in central africa than those who have immigrated to the USA.

Question 4

Tobacco causes

Answer 4

24% in lung kidney and bladder cancer

Question 5

Diet low in veg, high in salt and nitrates

Answer 5

5% of stomach and esophogus

Question 6

diet high in fat and low fibre
also includes fried and broiled foods

Answer 6

37% of bowel, pancreas, prostate and breast cancer

Question 7

Tobacco and alcohol

Answer 7

2% of mouth and throat

Question 8

Tumor initiators

Answer 8

They are mutagens that are either physical or chemical
-Many chemicals in the liver are unreactive but are converted into mutagens via cytochrome P450 metabolism and would not cause cancer if just given to cells

Question 9

E.Mutagens

Answer 9

Diazomethane, aromatic amines, nitrosamines

Question 10

Test for mutagens

Answer 10

Ames test

Question 11

Tumor promoters

Answer 11

They promote changes to the intracellular or extracellular environment of the damaged cell to promote tumor formation
-They require tumor initiators to induce tumor
-Chronic inflammation and repair are sufficient to promote tumor formation of mutated cells as the chemicals stimulate damaged cells to grow

Question 12

E.Tumor promoter

Answer 12

Phorbol esters are a class of compounds that activate Protein Kinase C
-This is a kinase that is activated by elevated calcium levels and Diacyl glycerol and promotes cell growth

Question 13

Viruses role in cancer history

Answer 13

Peyton rouse showed that the Rous sarcoma virus that was extracted from chicken tumors could transmit cancer to health chickens
-the v-src gene in the RSV is a oncogene that pushes cells into uncontrolled mitosis and transformation

Question 14

how much cancer do viruses cause

Answer 14

20% of all cancers

Question 15

HPV

Answer 15

-Human Pappiloma virus
-They infect cutaneous and mucosal epithelia
-HPV 16 is a HR (high risk genotype) that causes 55% of cervical cancers
-HPV 18 causes 18% of cases of cancer from HPV

Question 16

classes of genes involved in cancer

Answer 16

-Oncogenes
-Tumor suppressor genes
-DNA maintanence genes

Question 17

Oncogenes

Answer 17

-Start as protooncogenes that promote cell survival
-Mutate into oncogenes that stimulate unregulated proliferation
-Only needs one mutated copy

Question 18

Tumor suppressor genes

Answer 18

Genes that when mutated, lose function and this loss of function pushes cells towards cancer phenotype
-Needs both copies to be mutated

Question 19

E. Viral transduction of oncogenes

Answer 19

-proto-oncogene c-SRC is transduced by RSV and it is a tyrosine kinase that is constitutively activated by virus
-v-src is an oncogene that pushes the cell into transformation

Question 20

Ras proteins

Answer 20

They are coded byproto-oncogenes that are mutated in cancer
-3 genes encode for them: HRas, KRas, NRas
-They are GTPases that function as molecular switches that regulate survival and proliferation pathways
-aMutations typically occur at 12, 13 and 61 codons

Question 21

Regulation of K-Ras

Answer 21

They have inherent GTase activity that degrade GTP into GDP to become inactive
-GTPase-activating proteins (GAPS): they increase the rate of GTP hydrolysis to GDP which switches it off
-Guanine nucleotide exchange factors (GEFs): facilitate the swopping of GDP for GTP in the G-protein which results in activation

Question 22

Mechanisms for conversion of proto-oncogenes into oncogenes

Answer 22

-Point mutations increasing the activity of the protein (Ras)
-Gene amplification events may result in extra copies of the gene (Myc oncogene)
-Chromosomal rearrangements may create a constitutively active fusion gene product or place the gene downstream of a promoter which results in dysregulated expression ( BCR-ABL1)

Question 23

Master cell regulator

Answer 23

-P53
-It responds to DNA damage and stress by controlling cell cycle, DNA repair, and apoptosis
-When activated, it acts as a transcription factor for may targets which changes due to context and type of stress

Question 24

DNA damage to P53

Answer 24

-Mutations in TP53 gene which causes loss of p53 tumor suppressor function
-P53 is regulated by MDM2 which targets the protein for degredation and suppresses transcription
-DNA damage releases the P53 from MDM2 and causes the P53 to migrate to the nucleus to act as a transcription factor
-Mutations result in loss of tumor suppressor function

Question 25

Retinoblastoma gene product

Answer 25

It regulates the cell cycle by acting as a checkpoint inhibitor that prevents dysregulated proliferation by preventing cell from entering S phase
-pRB binds to TF E2F which prevents transcription of genes that push cell into S phase
-It is phosphorylated and inactivated by an active CDK4-cyclin D complex which is inactivated by p16
-Cancer cells inactivate this gene or overexpress CDK4-cyclin D

Question 26

HPV effect on p53 and pRB

Answer 26

-E6 and E7 proteins bind to p53 and pRB respectively

Question 27

AKT effect on cancer

Answer 27

-It is a kinase that causes increased glucose uptake and overall metabolic function when mutated
this provides increased energy for cancer