Cancer 2 (02.25) Flashcards
1
Q
Predominant cause of most sporadic cancers
A
Environmental factors
2
Q
2 functions of beta-catenin
A
Binds E-Cadherin; Activate cell proliferation in nucleus via WNT signaling pathway
3
Q
3 disorders involving defects in homologous recombination repair
A
Bloom Syndrome, Ataxia-Telangiectasia, Falconi Anemia
4
Q
3 leading causes of cancer death
A
Carcinomas of Lung, Colon, and Breast
5
Q
3 members of BH3-only proteins
A
BAD, BID, and PUMA
6
Q
4 key regulators of the cell cycle
A
CDKN2A, Cyclin D, CDK4, Rb
7
Q
Action of APC gene
A
Cytoplasmic protein whose dominant function is to regulate intracellular levels of beta-catenin
8
Q
Action of ATM
A
Protein kinase that, when activated, releases p53 from MDM2
9
Q
Action of BH3-only proteins
A
Regulate balance between pro- and anti-apoptotic members of BCL2 family
10
Q
Action of Caspase-3
A
Executioner caspase: Cleaves DNA and other substrates
11
Q
Action of CDKN1A (p21)
A
Inhibits cyclin-CDK complexes –> Prevents activation of Rb –> Arrests cells in G1 phase
12
Q
Action of Cytochrome C
A
Binds APAF-1 and activates Caspase-9
13
Q
Action of Destruction complex containing APC
A
Degrade cytoplasmic beta-catenin –> Inhibit WNT signaling
14
Q
Action of FLIP
A
Bind death-inducing signaling complex and prevent activation of caspase-8
15
Q
Action of HPV E7 protein
A
binds to hypophosphorylated Rb, preventing it from inhibiting E2F transcription factors
16
Q
Action of hypophosphorylated Rb
A
Inhibits E2F family of transcription factors –> preventing transcription of Cycline E –> Prevent dna replication
17
Q
Action of MDM2
A
Associates with p53, targets for destruction
18
Q
Action of NF2 (merlin)
A
Facilitates E-cadherin mediated contact inhibiton
19
Q
Action of VHL
A
Binds HIF-1 in normoxic environment for destruction
20
Q
Activation of __ drives transcription of CDKN1A (p21)
A
p53
21
Q
Almost all cancers have a disabled
A
G1 checkpoint (RB, CycD, CDK4, CDKN2A)
22
Q
Anti-apoptotic members of BCL2 family
A
BCL2 and BCL-XL
23
Q
APC is what type of gene
A
tumor suppressor
24
Q
Autosomal dominant cancer syndrome: APC
A
Familial Adenomatous Polyposis/Colon Cancer
25
Autosomal dominant cancer syndrome: MEN1, RET
Multiple Endocrine Neoplasia 1 and 2
26
Autosomal dominant cancer syndrome: MSH2, MLH1, MSH6
Hereditary Nonpolyposis Colon Cancer
27
Autosomal dominant cancer syndrome: p16INK4A
Melanoma
28
Autosomal dominant cancer syndrome: PATCH
Nevoid Basal Cell Carcinoma Syndrome
29
Autosomal dominant hereditary cancer syndromes are typically a mutation of a
Tumor suppresor gene
30
Autosomal recessive hereditary cancer syndromes are typically a mutation of
DNA repair
31
Autosomal Recessive Syndromes of Defective DNA Repair
Xeroderma Pigmentosa, Ataxia-Telangiectasia, Bloom Syndrome, Fanconi Anemia
32
Beta-catenin is an important component of the ___ pathway
WNT signaling
33
BRCA1/2 are often inactivated in sporadic cancers
FALSE
34
BRCA1/2 seem to function in __ pathway
homologous recombination DNA repair
35
BRCA2 was shown to bind to ___
RAD51, a protein required for homologous recombination
36
Cardinal feature of NF1-associated tumors
Ras hyperactivity
37
CDKN2A is seen in 75% of
Pancreatic carcinomas
38
CDKN2A should make you think
(1) Pancreatic carcinoma; (2) GBM
39
Cells that lack BRCA1/2 develop
chromosomal breaks and severe aneuploidy
40
Characteristic finding in genome of patients with mismatch repair defects
Microsatellite Instability (MSI)
41
Checkpoint mediated by Rb
G1-S
42
Clear cytoplasm in squamous epithelium due to glycogen is a sign of
maturation
43
Clear cytoplasm in squamous epithelium is due to
Glycogen
44
Cytoplasmic portion of E-Cadherin binds
Beta-Catenin
45
Cytoplasmic protein whose dominant function is to regulate intracellular levels of beta-catenin
Action of APC gene
46
E-cadherin mediates
cell-cell contact in epithelial layers
47
Endometrial hyperplasia and dysplasia is a risk factor for
Endometrial Carcinoma
48
Facilitates E-cadherin mediated contact inhibiton
Action of NF2 (merlin)
49
Features that characterize familial cancers
(1) Early age at onset; (2) Tumors arising in 1 or more close relatives; (3) Multiple or Bilateral Tumors
50
Function of ATM
Protein Kinase important in recognizing DNA damage by ionizing radiation and initiating p53 activation
51
Function of Beclin-1
Induces autophagy; member of BH3 family
52
Function of MMP-9 in cancer
Cleaves Type IV Collagen; Stimulates release of VEGF from ECM-sequesterd pools
53
Function of SNAIL and TWIST transcription factors in extravisation
Suppress E-cadherin
54
Function of TSP-1
Prototypical angiogenesis inhibitor
55
Gap1 (G1) is between
Mitosis and DNA replication (S)
56
Gap2 (G2) is between
DNA replication (S) and Mitosis
57
Glucose carbone use is achieved by
shunting pyruvate toward the biosynthetic pathways at the expense of ox phos and ATP generation
58
Hereditary Breast Cancer Syndromes are what percent of breast cancers
5%
59
HNPCC syndrome results from
defects in genes involved in DNA mismatch repair
60
How are cell-cell contacts lost?
Inactivation of E-cadherin
61
How are tumor cell "loosened"?
Inactivation of E-cadherin which holds cells together
62
How do BH3-only molecules affect apoptosis
Activate by tilting balance in favor of pro-apoptotic molecules
63
How do cancers inactivate E-cadherin
(1) Mutation; (2) Activation of beta-catenin; (3) Inappropriate SNAIL or TWIST expression
64
How do endothelial cells affect tumor growth
Secrete growth factors: ILGF, PDGF, GM-CSF
65
How does E-Cadherin transmit antigrowth signals
Sequestering Beta-catenin
66
How is the extrinsic (death receptor) pathway initiated
TNF receptor, such as CD95 (Fas), is bound to its ligand CD95L, leading to trimerization of receptor and cytoplasmic death domains, which attract FADD
67
How is tumor vasculature abnormal
Vessels are leaky and dilated; Haphazard pattern of connection
68
How it beta-catenin activated
APC destruction complex is disbanded, allowing beta-catenin to translocate to nucleus
69
Importance of hereditary influence on cancers?
Subtle and sometimes indirect (5-10%)
70
In 100% of pancreatic cancers and 83% of colon cancers, a least one component of the __ pathway is mutated
TGF-Beta
71
In 85% of follicular B cell lymphomas, __ is activated by translocation
BCL-2 (anti-apoptotic)
72
In many late-stage tumors, TGF-beta signaling activates
epithelial-to-mesenchymal transition
73
In most normal cells, TGF-Beta is a
potent inhibitor of proliferation
74
In what pathway is SMAD4 involved
TGF-Beta anti-proliferative pathway
75
Leukoplakia of the oral cavity, vulva, or penis may progress to
Squamous Cell Carcinoma
76
Level of beta-catenin in quiescent cells
Degraded by a destruction complex, of which APC is an integral part
77
Location of Rb gene
13q14
78
Maximum distance that nutrients can diffuse from blood vessels
1-2 mm
79
miRNAs activated by p53 inhibit translation of
pro-proliferative (cyclins) and anti-apoptotic genes (BCL2)
80
More than 70% of human cancers have defect in
TP53
81
Most cancer deaths occur between what ages
55-75
82
MSI can be detected in __ of sporadic cancers
15%
83
Mutaion in APC allows
beta-catenin to translocate to nucleus --> Proliferation
84
Mutation inactivation of SMAD genes
No TGF-beta signaling --> Proliferation
85
Mutational activation of CDK4 or overexpression of Cycline D mimics
Rb mutational inactivation --> Escape from checkpoint
86
Mutational inactivation of CDKIs would
drive cell cycle by unregulated activation of cyclins and CDKs
87
Neurofibromin is a negative regulator of
Ras
88
Once a cell cross the __ checkpoint, it is obligated to complete mitosis
G1
89
p53-mediated cell cycle arrest is caused mainly by
transcription of CDKN1A (p21)
90
Pallisading necrosis should make you think
GBM
91
Pap smear: Less cytoplams, more nuclei =
High grade
92
Patients w/ Xeroderma Pigmentosa are unable to repair __ after UV
Pyrimidine dimers
93
Patients with familial retinoblastoma are also at increased risk for
Osteosarcomas and soft tissue sarcomas
94
Primary function of SNAIL and TWIST
Promote EMT (downregulate E-cadherin)
95
Primary source of carbons used for synthesis of lipids in dividing cancer cells
Glucose
96
Pro-apoptotic members of BCL2 family
BAX and BAK
97
Prototypical angiogenesis inhibitor
TSP-1
98
Recommended treatment for paitent with hereditary breast and ovarian cancer syndrome
Bilateral mastectomies and Salpingo-oophorectomies
99
Relation of p53 to angiogenesis
Induces synthesis of TSP-1, an angiogenesis inhibitor
100
Role of BCL2 overactivation in cancer
Anti-apoptotic
101
Somatic loss of both alleles of APC gene is seen in
70% of sporadic colon cancers
102
T/F: Benign tumors are generally considered precancerous
FALSE, some exceptions
103
T/F: E-cadherin function is amplified in almost all tumors
False, lost
104
T/F: Familial cancers are associated with specific marker phenotypes
FALSE
105
T/F: Most preneoplastic lesions develop into cancer
FALSE
106
The expression of Cyclin E is dependent on
the E2F family of transcription factors
107
The geographic variation of cancer incidence results mostly from
Different Environmental Exposures
108
The initiation of DNA replication requires activity of
Cyclin E/CDK2 complexes
109
Type of DNA repair defective in Xeroderma Pigmentosa
Nucleotide Excision Repair
110
Upregulation of PDGF-PDGF receptor occurs in
brain tumors
111
VEGF also increases expression of ligands that activate
Notch signaling pathway --> Regulates branching and density of new vessels
112
Villous Adenomas may progress to
Colorectal Carcinoma
113
What do Angiostatin, Endostatin, and Vasculostatin have in common
potent angiogenesis inhibitors
114
What does FADD recruit in extrinsic pathway
Procaspase-8 --> Caspase-8 --> Caspase-3
115
What happens to HIF-1 in hypoxic setting
Not bound by VHL, translocates to nucleus to activate VEGF
116
What happens to HIF-1 in normoxic setting
Bound by VHL and destroyed
117
What induces synthesis of TSP-1
normal p53
118
What inhibits E2F family of transcription factors
Hypophosphorylated Rb
119
What is most important regulation of Rb
G1/S Checkpoint
120
What percentage of retinoblastomas are sporadic
60%
121
What phosphorylates Rb
Growth factors --> CyclinD/CDK4/6 --> Phosphorylate Rb
122
What produces TSP-1
Stromal Fibroblasts
123
What releases growth factors from Ecm and generates chemotactic and angiogenic fragments from cleavage of ECM glycoproteins
Proteolytic Enzymes
124
Which Cyclin stimulates Dna replication
Cyclin E (inhibited by hypophosphorylated Rb)
125
Which is more fata, lung or breast cancer?
Lung
126
Which is more fatal, lung or prostate cancer?
Lung
127
Which pathway involves Caspase-9
Intrinsic
128
Why is VHL a tumor suppressor
Binds and degrades HIF-1, preventing VEGF transcription and neovascularization
129
With loss of APC, __ degradation is prevented
beta-catenin --> WNT signaling activated
