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Biochem IV > Cancer > Flashcards

Cancer Flashcards

1
Q

The six hallmarks allow a cell to be transformed into what type of cancer?

A

Invasive

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2
Q

Gain of function mutations are typically what?

A

dominant

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3
Q

HER is a receptor for what?

A

epidermal growth factor

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4
Q

Does the HER2 family of receptors function as homodimers or heterodimers?

A

either

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5
Q

HER1 or ErbB1 refer to what?

A

EGFR

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6
Q

How is ErbB1 converted into a constitutively active form?

A

mutation removes ligand binding domain that results in activation

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7
Q

How is HER2 converted into a constitutively active form?

A

a point mutation in TMSR that allows for receptor dimerization

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8
Q

Pancreatic cancers often feature what type of cell signaling mutation?

A

Ras mutations

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9
Q

Burkitt’s Lymphoma results from inappropriate activity of what cell signaling molecule?

A

c-Myc

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10
Q

What type of translocation happens to c-Myc in Burkitt’s Lymphoma?

A

chromosome 8 to chromosome 14

c-Myc near antibody heavy chains

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11
Q

When does this translocation occur?

A

during maturation of antibody producing B-cells

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12
Q

Are mutations in tumor suppressor genes typically dominant or recessive?

A

recessive

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13
Q

What proteins must be liberated from Rb in order to induce cell cycle progression?

A

E2F

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14
Q

What protein is p53 generally associated with? What will this do?

A

MDM2

act as an E3 ubiquitin ligase

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15
Q

What proteins can phosphorylate p53? What will this do to the association of p53 with mdm2?

A

ATM or ATR

cause dissociation of p53 from mdm2

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16
Q

What is a key protein upregulated by p53?

A

p21-CIP1

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17
Q

What is the function of p21-CIP1?

A

cell cycle arrest

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18
Q

If there is too much DNA damage to overcome, what can p53 do to cell growth?

A

signal senescence or apoptosis

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19
Q

What complex is the active form of p53 in?

A

homotetramer

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20
Q

Li Fraumeni patients have a mutant allele for what what gene? This disrupts the formation of what?

A

TP53

TP53 tetramer

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21
Q

What two proteins do the HPV produce?

A

E6 and E7

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22
Q

What is the function of E6?

A

inhibits p53

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23
Q

What is the function of E7?

A

inhibits Rb

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24
Q

Neurofibromatosis occurs due to loss of what gene?

A

NF1

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25
Q

NF1 gene encodes what protein?

A

neurofibromin

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26
Q

What is the function of neurofibromin?

A

to accelerate the rate at which Ras hydrolyzes GTP

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27
Q

Development of neurofibromatosis follows what kind of mechanism?

A

two-hit

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28
Q

What is the role of BRCA2?

A

homologous recombination

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29
Q

Both BRCA1 and BRCA2 are important in the repair of what?

A

double-stranded DNA breaks

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30
Q

Other than homologous recombination, what else is BRCA1 involved in?

A

G1/2 and G2/M checkpoint

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31
Q

Regarding homologous recombination, what do the roles of BRCA1 and BRCA2 appear to be?

A

delivery of effector proteins to sites of double-stranded DNA breaks

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32
Q

What other function does BRCA1 possess?

A

E3 ubiquitin ligase

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33
Q

What does methylation of a gene do?

A

makes it transcriptionally silent

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34
Q

What is the sequence of telomeres?

A

TTAGGG

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35
Q

Short telomeres appear to be recognized as what?

A

double-stranded DNA breaks

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36
Q

Cells implicated in a breakage/fusion/bridge cycle tend to up-regulate what protein?

A

telomerase

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37
Q

What is an important signal relating to sustained angiogenesis?

A

hypoxia

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38
Q

Hypoxia stimulates an oxygen sensitive txn factor known as?

A

HIF-1ab

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39
Q

During normoxia, how is HIF-1ab regulated?

A

hydroxylated by a proline hydroxylase

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40
Q

How do the hydroxylated prolines of HIF-1ab serve to control its regulation?

A

serve to recruit E3 ubiquitin ligase

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41
Q

What happens to these hydroxylated residues during anoxia? What does this entail?

A

the residues are not hydroxylated

HIF-1ab is not targeted for degradation

42
Q

How does HIF promote angiogenesis?

A

HIF-1a and HIF-1b for a dimer and activate VEGF

43
Q

What proteins normally hold epithelial cells together?

A

E-Cadherin

44
Q

What two steps must a cell accomplish to successfully metastisize?

A

tissue invasion and extravasation

45
Q

What product, secreted by tumor cells, breaks down the basement membrane?

A

matrix metalloproteases

46
Q

What is intravasation?

A

tumor cell entering the bloodstream

47
Q

What degradation components of the basement membrane signal migration?

A

collagen IV and laminin

48
Q

What is extravasation?

A

exit from the bloodstream

49
Q

What is an adenoma?

A

benign tumor

50
Q

What is a carcinoma?

A

malignant tumor

51
Q

Patients with FAP develop what kind of colon cancer?

A

thousands of adenomatous polyps

52
Q

FAP results from mutation of what gene?

A

adenomatous polyposis coli (APC)

53
Q

beta-catenin stimulates the txn of what two genes?

A

cyclin D and Myc

54
Q

When WNT binds to its ligand, what happens to beta-catenin?

A

it is liberated from proteasomal degradation

55
Q

In the absence of WNT ligand, what happens to beta-catenin?

A

beta-catenin is targeted for proteasomal degradation

56
Q

How do mutations in APC affect WNT signaling?

A

WNT signaling is constitutively active

57
Q

What is the role of APC regarding WNT and beta-catenin?

A

to form a destruction complex between APC/WNT/beta-catenin

58
Q

HNPCC patients have defects in what pathway?

A

DNA mismatch repair

59
Q

What two genes are involved in the mismatch repair defects in HNPCC patients?

A

MSH2 and MLH1

60
Q

What is the function of MSH2?

A

to identify mismatch repairs

61
Q

What is the function of MLH1?

A

to fix the mismatch repairs

62
Q

What chromosomes are involved in the Philadelphia Chromosome? What genes are affected?

A

9 and 22

BCR and ABL1

63
Q

What product does the ABL1 gene encode?

A

soluble protein tyrosine kinase

64
Q

What condition features a the philadelphia chromosome?

A

chronic myeloid leukemia

65
Q

What drug is used to treat chronic myeloid leukemia?

A

imatinib (Gleevec)

66
Q

What are two additional Bcr-Abl drugs used to treat chronic myeloid leukemia?

A

nilotinib and dasatinib

67
Q

How do imanitib, nilotinib and dasabitib function?

A

Bcl-Abl tyrosine kinase inhibitor

68
Q

What is HER2/Neu?

A

receptor tyrosine kinase

69
Q

What type of receptor is the EGFR? What is another name for this receptor?

A

receptor tyrosine kinase

ErbB1

70
Q

What mutations occurs to make ErbB1 constitutively active?

A

mutation that removes extracellular ligand binding domain

71
Q

What is the mutation that renders HER2 active?

A

point mutation that causes dimerization/autophosphorylation in the absence of ligand

72
Q

What cyclins do c-Fos and c-Myc stimulate production of?

A

Mid and Late phase G1

73
Q

Burkitt’s Lymphoma results from inappropriate activitity of what protein?

A

Myc

74
Q

What type of mutation takes place in Burkitt’s Lymphoma? What does this do to Myc?

A

translocation

increase in expression of Myc

75
Q

What chromosomes are involved in Burkitt’s Lymphoma?

A

8 and 14

76
Q

The active form of p53 resides in what sort of complex?

A

homotetramer

77
Q

Li-Fraumeni patients have a mutated copy of what gene? What does this cause to the protein product?

A

TP53

inability to form homotetramer

78
Q

What are the apparent functions of BRCA1 and BRCA2 regarding double stranded breaks?

A

to deliver effector proteins to heal double-stranded breaks

79
Q

What is the sequence of telomeres?

A

TTAGGG

80
Q

Telomeres prevent shortening of what strand, the lagging or the leading strand?

A

lagging

81
Q

Short telomeres are detected as what?

A

double-stranded DNA breaks

82
Q

The lack of telomeres allows fusion of what?

A

sister chromatids

83
Q

What is the function of E-cadherins?

A

hold epithelial cells together

84
Q

FAP results from a mutation in what gene?

A

adenomatous polyposis coli

85
Q

Where do Lynch syndrome mutations appear to congregate?

A

Microsatellite Repeats

86
Q

What is microsatellite instability?

A

defective mismatch repair mutations leads

87
Q

What protein that is involved in regulation of cell growth contains microsatellite repeats?

A

Bax

88
Q

What is the protein product of ABL1?

A

soluble protein tyrosine kinase

89
Q

What is rituximab used to treat?

A

non-Hodgkins Lymphoma

90
Q

What chromosomes are involved in Burkitt’s Lymphoma?

A

8 and 14

91
Q

What DNA binding protein is implicated in Burkitt’s Lymphoma?

A

Myc

92
Q

What promoter does Myc aberrantly use in Burkitt’s Lymphoma?

A

antibody heavy chain

93
Q

What protein is dissociated from p53 upon its dissociation?

A

Mdm2

94
Q

Active p53 is in what kind of complex?

A

homotetramer

95
Q

How does LiFraumeni disrupt function of p53?

A

inhibits formation of tetramer

96
Q

BRCA1 and BRCA2 are implicated in what DNA repair mechanism?

A

homologous recombination

97
Q

Homologous recombination is involved in fixing what type of DNA breaks?

A

double-stranded

98
Q

Short telomeres are recognized as what?

A

DNA double-stranded breaks

99
Q

What are two components of basement degradation? What do these proteins doe regarding metastasis?

A

collagen IV and laminin

promote metastasis

100
Q

Activation of WNT pathway results in the production of what two mitogenic proteins?

A

Myc and cyclin D

101
Q

FAP patients often possess an oncogenic form of what cellular protein?

A

Ras

102
Q

HNPCC defects occur in what kind of repeats?

A

microsatellite repeats

Biochem IV (6 decks)

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