Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

M1 > Molecular Mechanisms of Cancer > Flashcards

Molecular Mechanisms of Cancer Flashcards

1
Q

Trophic factor of primary cells

A

“Bad” - if trophic factor is removed - cell undergoes apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Cyclin and CDK control of cell division

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

E2F transcription factor

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The cell cycle can be arrested due to DNA damage in what stage(s) of the cell cycle?

A

G1 and G2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Maintenance methylase

A

Ensures that the daughter DNA strand has the same methylation pattern as parent strand - so that same genes will be expressed in daughter cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Burkitt’s lymphoma

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do transforming retroviruses produce cancers?

A

By carrying extraviral DNA that encodes and oncogene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do DNA viruses cause transformation?

A

They are sometimes, accidentally, incorporated into the host cell genome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List common tumor supressor genes

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Tumor supressor gene that functions as a transcription factor

A

p53

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Series of mutations associated with colon cancer

A
  1. Loss of APC
  2. Activation of K-ras
  3. Loss of DCC
  4. Loss of p53
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Function of Mdm2

A

Prevents p53 activity in the absencce of DNA damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

The majority of mutations in p53 are located in what region?

A

DNA binding domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Caspases

A

Cysteine proteases that set apoptosis in motion

Induce apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Presence of trophic factor

A

PI-3 kinase activates Akt, which phosphorylates bad.

P-Bad is bound by a cytosolic protein, 14-3-3, preventing Bad from inhibiting the antiapoptotitc Bcl-2/Bcl-xl proteins.

Bcl-2/Bcl-xl inhibit Bax channel formation, so cytochrome C stays inside the mitochondria and caspases remain in the inactive (procaspase) forms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Absence of trophic factor

A

Bad (soluble pro-apoptotic protein) binds to and inhibits anti-apoptotis proteins (Bcl-2 and Bcl-x) in the mitochondrial membrane.

This allows a membrane-bound pro-apoptotic protein, Bax, to form channels in the outer mitochondrial membrane leading ot the release of cytochrome C.

In the cytosol, cytochrome C interacts with adapter protein, Apaf-1, and promotes activation of the caspase cascade - leads to cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The cell cycle

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Entry of cells into S and M phases

A

Strictly regulated

Dependent upon supplies to initiate DNA synthesis and complete replication of the genome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Restriction point

A

Major checkpoint late in G1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Mitotic cyclins

A

Clyclins A and B bind during the G2 to M transition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

G1 cyclins

A

Cyclins D and E bind to CDK’s during G1 to S transition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Regulation of cyclin-CDK complexes

A

CDK inhibitor proteins (CKIs)

i.e. p21Cip, p27Kip, and p16Ink4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

E2F

A

Activation is an early event in the transition from G1 to S phase - transcription factor that induces expression of genes needed in S phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Retinoblastoma protein (Rb)

A

Inhibitor of cell proliferation - tumor supressor

Hypo-phosphorylated Rb binds to and inactivates E2F arresting cells in G1 phase

CDK in mid-late G1 (and during S) hyper-phosphorylate Rb causing it to resease E2F (promotes transition of cells from G1 to S

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Cell arrest in G1 vs. G2

A

G1 - prevent copying of damaged bases during DNA synthesis

G2 - alows DNA double stranded breaks to be repaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Sensors of DNA damage

A

Include ATR and ATM

ATR - ataxia talangiectasia and Rad3-related

ATM - ataxia telangiectasia mutated

Both ATM and ATR have kinase activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

P53

A

Transcirption factor necessary for cell cycle arrest due to damaged DNA

Normally p53 is unstable and degraded quickly, so levels are kept very low

DNA damage leads to phosphorylation of p53 - stabilizes p53 - allowing it to accumulate and stimulate transcription of a cyclin-CDK inhibitor gene (21CIP) p21 inhibits cyclin-Cdk activity to halt cell cycle progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What allows for a small number of transcription factors to regulate a wide variety of genes, contributing to cellular diversty

A

Combinational gene control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Maintenance methylase

A

Methylates CG sequences on the duaghter strands which are paired to methylated CG sequences of the parental strand, so methylation pattern is inherited by daughter cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What can impair fetal DNA methylation during embryogenesis?

A

Acetaldehyde from alcohol metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Malignant tumors

A

High nucleus to cytoplasm ratio, prominent nucleoli, many mitoses, and relatively little specialized structure

Presence of invading cells in otherwise normal tissue section is the most diagnostic indication of malignancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Cancer can result from the mutations in what classes of proteins?

A
  1. Growth factors and receptors
  2. Signal transduction proteins
  3. Transcription factors
  4. Cell-cycle control proteins
  5. Apoptosis proteins
  6. DNA-repair proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Gain of function mutations

A

pro-oncogenes to oncogenes

Act dominant, only one altered allele will produce and effect in the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Loss of function mutations

A

Mutations in tumor supressor genes

They act recessive (usually), both alleles have to be inactivated before the phenotypic effect is produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Tumor supressor genes

A

Function to halt cell division, induce apoptosis, or repair damaged DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Coversion of proto-oncogene to an oncogene

A

Spontaneous or chemical induced GOF mutations that result in a constitutively active protein

Localized duplication (gene amplification) of a region of DNA containing a proto-oncogene - > too much gene expressed

Chromosomal translocations and DNA rearrangements that bring a frowth regulatory gene under control of a different promoter causing over expression of gene

Or produced an actively transcribed fusion gene (part of gene A is combined with part of gene B) resulting in a hyperactive fusion protein

Infection by tumor causing viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

The neu receptor

A

aka ErbB-2 or HER2 (human epidermal growth factor receptor 2) can undergo mutation that alters a single amino acid in the transmemebrane region, resulting in an RTK with constitutive tyrosine kinase activity

37
Q

Herceptin

A

mAb directed against HER-2 receptor

38
Q

Loss of the EGF-binding domain of HER1

A

Produces a truncated protein with unregulated tyrosine kinase activity

These cells are stimulated to proliferate even at concentrations of EGF that do not stimulate normal cells

38
Q

Cetuximab

A

mAb that targets HER1 and is used to treat certain cancers, including colorectal and head and neck cancers.

By inhibiting HER1, it helps to slow down or stop the growth of cancer cells.

39
Q

Ras signaling pathway

Diagram

A
40
Q

Mutations in Ras that reduce its GTPase activity

A

Ras stays active longer than normal - oncogenic

41
Q

GOF mutation in guanine exchange factors (GEFs)

A

Result in hyperstimulation of Ras signaling

42
Q

LOF mutations in GTPase activating proteins (GAPs)

A

Will prolong Ras signaling

GAPs are tumor supressors

NF1 encodes a GAP that accelerates GTP hydrolysis of Ras

Loss of NF1 function allows Ras to remain in its activated GTP-bound state longer than normal

Individuals with neurofibromatosis inherit one mutant NF1 allele, but do not develop neurofibromas until a second somatic mutation occurs in the other NF1 allele of a cell. The loss of both functional NF1 alleles in the same cell leads to uncontrolled cell growth and the formation of tumors, such a neurofibromas

43
Q

Proto-oncogenes of the restriction point

A

Cyclin D1 becomes an oncogene when it is overexpressed or amplified, leading to excessive activation of the cell cycle. This drives uncontrolled cell division, contributing to cancer development by bypassing the normal regulatory mechanisms.

44
Q

Retinoblastoma gene

A

RB1is a tumor suppressor, when RB is mutated, E2F is unchecked, leading to uncontrolled cell division and contributing to the development of retinoblastomas. RB is a tumor suppressor; loss of both alleles is needed in the cell for transformation

45
Q

SV40 DNA tumor virus

A

Encodes a protein called large T antigen that inhibits two tumor suppressor proteins, Rb and p53, that normally halt cell proliferation.

Large T causes tumors in primates

46
Q

Human Papillomavirus (HPV)

A

Expresses two separate proteins; E6 which binds p53, and E7 which binds Rb. If the E6/7 viral genes accidentally integrate into the host genome they can be overproduced in an unregulated fashion resulting in cancer

47
Q

Acute transforming retroviruses

A

When a pro-virus integrated next to a proto-oncogene. As the viral genome was copied, part of the proto-oncogene was also copied due to read-through transcription.

The proto-oncogene then underwent a GOF mutation that converted it into an oncogene

48
Q

Rous Sarcoma Virus (RSV)

A

Causes fibrosarcomas (in chickens, not humans). RSH was the first characterized retrovirus

Three structural genes (gag, pol, env, and v-src)

V-src is required for cancer induction

49
Q
A
50
Q

c-src

A

proto-oncogene nearly identical to v-src which is a protein-tyrosine kinase

v-Src is an oncogene - truncated or mutated at the C-terminus which removes regulatory domain in c-src

51
Q

Human T-cell lymphotropic Virus type 1 (HTLV-1)

A

A retrovirus that cuases adult T-cell leukemia/lymphoma (ATLL). HTLV-1 contains a regulatory gene, tax, that is a transcriptional activator.

Tax disrupts a cellular tumor suppressor pathway and enhances the expression of proto-oncogenes contributing to transformation

52
Q

Chromosomal transolacations that cause transformations

A
  1. Placing a proto-oncogene under control of a different gene promoter leading to over expression - Burkitt’s lymphoma
  2. Creating a fusion (frankenstein) protein - Chronic myelongeous leukemia
53
Q

Burkitt’s lymphoma

A

B-cell non-Hodgkin lymphoma that results from t(8:14)

c-myc - proto-oncogene, on ch 8 is placed next to an immunoglobulin gene promoter on ch 14. Since immunoglobulins are highly expressed in B-cells, c-myc is now highly expressed. C-myc activateds expression of genes that drive cells through the G1-S transition.

54
Q

Chronic myelogenous leukemia (CML)

A

t(9:22)

ch 9 carries thec-abl gene - tyrosine kinase

Flanking region on ch22 carriers the N-terminus of the BCR gene

BCR-Abl fusion protein has consitutive tyrosine kinase activity resulting in phosphorylation of proteins that are not normally substrates of Abl. These proteins are activated to drive excessive proliferation of a clone of hematopoeitic cells in bone marrow.

55
Q

Classes of proteins that function as tumor supressors

A

Checkpoint control proteins that halt cell cycle progression (i.e. Rb and p53)

CDK inhibitor proteins (p16 and p21CIP)

Receptors for hormones the inhibit cell proliferation (i.e. TGF-beta receptors)

Pro-apoptotic proteins

DNA repair enzymes

56
Q

Prominent Tumor Suppressors

A

Retinoblastoma - spontaneous vs hereditary

P53

Adenomatous polyposis coli (APC gene)

Neurofibromatosis type 1 (NF1 gene)

57
Q

Genomic instability

A

When cells bypass senscence and telomeres become critically short

Exposed chromosome ends are seen as DNA breaks and the cell tries to repair these

Creates a highly mutagenic environment

58
Q

PD-1 Receptor

A

Programmed Death-1

Receptor primarily expressed on activated T cells

59
Q

PD-L1

A

Programmed death ligand-1

Expressed on various healthy/normal cell types

Many cancers upregulate PD-L1 to hide from immune system

60
Q

What tumor supressor gene is negative-dominant?

A

p53

61
Q

Familial adenomatous polyposis

A
  1. LOF of adenomatous polyposis coli (APC) gene (a series of mutations, including activation of Ras - specifically K-ras)
  2. Loss of another TS gene - deleted in colon carcinoma (DCC) gene
  3. Loss of p53
62
Q

Murine mAbs

A

100% mouse proteins

High risk of hypersensitivity rx’ns

Suffix -omab

63
Q

Chimeric mAbs

A

~65% human

suffix = -ximab

64
Q

Humanized mAbs

A

~95% human

suffx = -zumab

65
Q

Human mAbs

A

100% human Abs

suffix = -mumab

Produced in humans or transgenic mice

66
Q

Imatinib mesylate (Gleevec)

A

1st cancer drug targeted to singal-transducing protein unique to cancer cells - (BCR-Abl)

Highly lethal to CML cells

2nd gen AbI kinase inhibitors - Dasatinib/Nilotinib are used against Gleevec-resistant tumors

67
Q

Small molecule inhibitors of the Tyr kinase activity of the EGF receptor (EGFR/HER1)

A

Geftinib (Iressa)

Erlotinib (Tarveca)

68
Q

mAb that binds human EGF receptor 2 (HER-2)

A

Trastuzumab (Herceptin)

69
Q

mAbs that bind to the external portion of EGFR to prevent binding of growth signals?

A

Cetuximab (Erbitux)

Panitumumab (Vectibix)

70
Q

What small molecule drug activates apoptosis of cancerous cells?

A

Bortezomib (Velcade)

Interferes with the proteasome - accumulates damaged proteins and triggers apoptosis

71
Q

What drugs target angiogenesis to Tx cancer?

A

Bevacizumab (Avastin) - binds to the VEGF to prevent angiogenesis

Sorafenib (Nexavar) and sunitinib (Sutent) - small molecule inhibitors of Tyr kinases involved in VEGF signaling

72
Q

Rituximab (Rituxan)

A

mAb that Tx’s certain B-cell nonHodgkin lymphomas

Recognizes CD20 on B cells, binds and triggers an immune response resulting in their destruction

73
Q

mAbs that bind to PD-1 and PD-L1

A

PD-1 is Tx’d by nivolumab (Opdivo)

PD-L1 Tx’d by pembrolizumab (Keytruda)

74
Q

The absence of growth factors (trophic factors) activates apoptosis by which of the following events?

A) Stimulation of Akt/PKB phosphorylation of Bad
B) Activating cleavage of proscaspases to mature caspases
C) Closing of Bax channels in the mitochondria
D) Increasing the binding of 14-3-3 pfogdin go Bad

A
75
Q

HPV may cause cervical cancer when ________

A

A part of the HPV genome inadverntently integrates into the host cell DNA and is averrantly expressed

HPV is a DNA virus

76
Q

Which protein functions to halt the cell cycle if damaged DNA is detected?

A

p53

77
Q

Gain of function mutation in the Ras proto-oncogene

A

Loss of GTPase activity

78
Q

What enzyme is responsible for preserving DNA methylation patterns during cell division in eukaryotes?

A

Maintenance methlase

79
Q

Sorafenib (Nexavar) is a treatment for metastatic renal cancer. What is its mechanism of action?

A

Inhibits tyrosine kinase activity of some receptor tyrosine kinases as well as a member of the MAP kinase pathway (MAKKK, Raf).

Sorafenib

80
Q

In the progression of familial adenomatous polyposis (FAP), what is the only gain of function mutation?

A

GOF of the K-Ras gene

81
Q

A patient with unresectable, locally advanced, metastatic non–small cell lung cancer undergoes treatment with Bevacizumumab (Avastin). After 6 cycles, tumor growth has halted. The most likely reason for the absence of disease progression in the patient is?

A

Reduction of tumor-induced angiogenesis due to blockade of Vascular Endothelial Growth Factor (VEGF) signaling.

82
Q

What familial cancer results from an inherited defect in the tumor suppressor gene, p53?

A

Li Fraumeni syndrome

83
Q

Both familial adenomatous polyposis colon cancer and smoking-related lung cancer often involve inaction of what gene?

A

p53

84
Q
A
85
Q
A
86
Q
A
87
Q
A
88
Q
A
89
Q
A

M1 (53 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions