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Flashcards in CA Deck (65):
1

What are the three types of genes that CA cells change?

1. proto onco genes
2. Tumor suppressor genes
3. caretaker genes

2

What is the mutational function of protoonco genes?

Converted to oncogenes that increase cell division

3

What is the mutational function of Tumor suppressor genes?

Will not turn off cell growth

4

What is the mutational function of Caretaker genes?

Do not prevent/repair DNA mutations

5

What are the 6 traits that a cell must obtain in order to become metastatic CA?

1. self sufficiency in growth
2. Insensitivity to antigrowth signals
3. Evading apoptosis
4. Limitless replicative potential
5. Sustained angiogenesis
6. Tissue invasion and metastasis

6

True or false: conversion of a proto-onco gene to an oncogene changes the activity of the protein itself

False- only results in excess production of the protein, or disrupts the normal control of the proteins function

7

The receptor for epidermal growth factor, which is a tyrosine kinase, is called what?

ErbB1 or HER2

8

What type of cascade does EGF act through?

MAP kinase cascade

9

How does ErbB1 become mutated?

remove the signal receptor

10

How does HER2 become mutated?

Dimerization in the absence of ligand due to changes in the plasma membrane spanning portion

11

How is Ras mutated?

point changes in amino acids leads to constant activation

12

How are c-Fos and c-Myc mutated?

Stabilization
(Normally they are unstable. DNA changes = stabilization)

13

What is Burkitt's lymphoma?

Increased in Myc activity

(translocation of Myc from chromosome 8 to chromosome 14= incrased transcription)

14

In general, are oncogenes on dominant alleles or recessive allele?

Dominant

15

In general, are tumor suppressor genes on dominant alleles or recessive allele?

Recessive

16

What needs to happen in the "two hit" model of CA proliferation in tumor suppressor gene for CA to develop?

Need one somatic mutation to develop CA cells

(Since tumor suppression genes are typically recessive genes, individuals can be carriers for mutant suppressor genes. Thus only a single allele needs to be mutated)

17

What is retinoblastoma?

CA caused by a mutation of the Rb protein gene, causing no Rb to be produced.

(note that this is a recessive allele in herditary form. Somatic form do not inherit any mutated allele.
Also, recall how Rb inhibits E2F)

18

What is the protein that associates with p53, makes it likely to be ubiquinated, and therefore likely to be degraded by proteosome?

Mdm2

19

What happens when p53 is phosphorylated by ATM or ATR? What molecule does p53 increase?

Stabilized
p21^CIP1

20

What is the most common genetic alteration in human CAs?

Mutations in p53

21

p53 is a homotetramer. How does this fact contribute to how mutations in the gene for p53 lead to cancer?

Makes it a dominant type of mutation

(a mutation will lead to incorrect protein in all tetramers since they are all the same)

22

What is Li-Fraumeni syndrome? What causes it?

Disease characterized by a propensity to develop a wide variety of tumors.
A mutation in the p53 allele.

23

HPV produces two proteins called what? What two proteins do they suppress?

E6 and E7
Both repress Rb, and p53

24

What causes neurofibromatosis?

Recessive gene mutation in NF1 that result in changes in neurofibromin

(neurofibromin functions to accelerate Ras hydrolysis--mutation= prolonged Ras)

25

What is the protein involved in neurofibromatosis? Symptoms?

Neurofibromin
CA cells around neuronal sheaths

26

What is the cause of HBOC syndrome? Is this a recessive or dominant trait?

Mutation in BRCA1 and BRCA2 genes.
Dominant

27

What are the BRCA genes used for?

Encoding proteins that repair double stranded DNA breaks

Also involved in E3 ubiuitin ligase

28

What are the two ways CA can develop from epigentic changes?

Silencing a gene (increased methylation)
Increasing the transcription of a gene (loss of methylation)

29

Why do cancer cells produce excess telomerases?

To avoid the inevitable breakage/fusion/bridge cycles that occur in somatic cells

30

What is the function of HIF-1aB?

An oxygen sensitive transcription factor that activates vascular endothelial growth facto (VEGF)

31

What is VEGF?

A protein stimulated by HIF-1aB that promotes the development of an angiogenic gradient, and thus new blood vessels

32

What is the signal for HIF-1aB to activate?

Hypoxia

(Oxygen causes a P-hydroxylase to ubiquinate HIF-1AB)

33

What is the function of E-adherin?

Hold epithelial cells together

34

What is the function of MMPs (matrix metalloproteases) in tumor cell metatasis?

Break down basement membrane holding the tumor cell down

35

What are the two chemical in the ECM that generate signals that stimulate the migration of tumor cells?

Collagen IV and laminin

36

What is the process by which tumor cells enter the circulation?

intravasation

37

What is extravasation?

The process by which tumor cells exit the bloodstream

38

What is FAP (familial adenomatous polypsis)?

Inherited condition where people develop thousands of adenomatous polyps in their colon.

39

If FAP is left untreated, what develops?

Colorectal carcinoma

40

What is the treatment for FAP?

Prophylactic colectomy

41

What gene is responsible for FAP?

APC-a tumor suppressor gene

42

The signal that APC regulates comes through what pathway?

WNT pathway

43

Which protein in the WNT pathway forms a "destruction complex" along with APC and other proteins to destroy itself when there is no WNT signals?

Beta-catenin

44

What is the function of beta-catenin?

increases the transcription of Myc and cyclin D

45

Is FAP a dominant or recessive disorder?

Recessive

46

What will happen if the second FAP allele is mutated?

Ras mutates to onconic Ras
p53 inactivation

47

How does the loss of APC lead to genomic mutations?

It plays a role in ensuring microtubles attach to the kinetichore of chromosomes

48

HNPCC is the result of a mutation in the DNA mismatch repair mechanism, leading to the formation of colorectal cancer. Which genes are mainly impacted?

MLH1 or MSH2

49

What is the function of the MSH2 protein?

Recognizes mismatches in DNA

50

What is the function of the MLH1 protein?

Repair DNA mismatch errors

51

What is microstaellite instability? What disease is it found in?

The propensity of microsatellite repeats to mutate
HNPCC

52

What is chronic myeloid leukemia?

CA that is the result of translocation of chromosomes 9 and 22.

53

The translocation of chromosomes 9 and 22 in chronic myeloid leukemia results in the fusion of what two genes? What protein does this combined gene produce?

BCR and ABL1
a Bcr-Abl tyrosine kinase

54

What is the action of the Bcr-Abl tyrosine kinase in Chronic myeloid leukemia?

Phosphorylates many target cells, potentially stimulating cell division--particularly in WBCs

55

What is the philidelphia chromosome? What disease is it a part of?

Combination of chromosome 9 and 22
Chronic myeloid leukemia

56

What are imatinib mesylate (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) used for? What is their mechanism of action?

Used in chronic myeloid leukemia
Inhibits the activity of Bcr-Abl tyrosine kinase

57

What is the function of trastuzumab (Herceptin)?

It is a monoclonal antibody that inhibits HER2/Neu in breast CA

58

What happens to the ErbB1 to turn it into an onoprotein?

Loss of the ligand binding domain

59

What happens to the HER2 (Neu) receptor to turn it into an oncoprotein?

Dimerization

60

What is the change in c-Myc that makes it oncogenic?

More stable

61

What is the change in c-fos that makes it oncogenic?

More stable

62

What is the chromosomal change in Burkitt's lymphoma?

c-Myc gene is translocated from chromosome 8 to chromosome 14

63

Are oncogenes usually dominant or recessive genes?

Dominant

64

Are tumor suppressor genes usually dominant or recessive genes?

Recessive

65

What is the gene that encodes p53?

TP53