Exam #4: Cancer Flashcards
1
Q
What are the six acquired capabilities of cancer cells?
A
1) Self-sufficiency in growth signals (oncogenes)
2) Insensitivity to antigrowth signals (tumor suppressors)
3) Evading apoptosis (mutation apoptotic pathway)
4) Limitless Replicative Potential (Telomerase)
5) Sustained Angiogenesis
6) Tissue invasion & metastasis
2
Q
Proto-oncogene vs. Oncogene
A
- Proto-oncogenes are genes associated with the control of cell division– they promote growth
- A mutated proto-oncogene is an oncogene causing excessive growth
- Gain of function mutation
- Dominant
- Analogous to gas pedal stuck on
3
Q
Tumor Suppressor Gene & Mutation
A
- Tumor suppressor genes normally inhibit growth
- Mutations inactivate the genes
- Recessive i.e. needs mutation in BOTH alleles
- Analogous to break failure
4
Q
Caretaker Gene & Mutation
A
- Function to protect the integrity of the genome e.g. DNA repair enzymes
- Mutation causes increased accumulation of DNA damage
5
Q
HER2
A
- Family of Epidermal Growth Factor Receptors (tyrosine kinase)
- Mutations convert into oncogene form
- Point mutation allows activation of receptor without ligand
- Generates Neu Oncoprotein
- Implicated in breast cancer
6
Q
Erb1
A
- Family of Epidermal Growth Factor Receptors (tyrosine kinase)
- Mutations convert into oncogene form
- Specifically, mutation deletes ligand binding domain
- Receptor is constitutively active without ligand
- Generates Erb1 Oncoprotein
7
Q
Ras Mutations
A
- G-protein that is normally activated by Sos in the MAP kinase signaling cascade
- Mutations generate a form of Ras that is constitutively active
- Specifically, mutations occur at amino acid positions 12, 13, or 16 & favor GTP binding
- Dominant
- Cancers include pancreas, large intestine, biliary tract, & skin
8
Q
Burkitt’s Lymphoma
A
- B-cell cancer
- Caused by c-Myc rearrangement from chromosome 8 to 14
- c-Myc now near control elements for antibody heavy chain
- Continual production of high levels of Myc in B-cells
9
Q
Two Hit Model
A
- 2 mutations required for tumorigenesis
- 1st mutation in germline (tumor suppressor) is inherited form parents & gives predisposition to cancer
- 2nd somatic mutation is spontaneously & necessary for tumorigenesis
10
Q
Retinoblastoma
A
- Malignancy of the retina seen in childhood
- Gene RB1 encodes Retinoblastoma protein, Rb, that normally inhibits cell cycle progression by binding E2F
- Hereditary vs. Sporadic
- Involved in numerous other cancers
11
Q
p53
A
- Normally unstable, stability increased by ATM/ATR phosphorylation
- Normal instability comes from association with Mdm2, which targets p53 for degradation
- Functions as homotetramer
- Encoded by TP53, most commonly mutated gene in cancer
- dominant negative mutations
12
Q
Li-Fraumeni Syndrome
A
- Heritable condition conferring susceptibility to many forms of cancer
- Dominant inheritance
- Caused by mutant TP53 allele i.e. disabled p53 tetramer
- DNA Damage Repair severely limited
- Early onset tumors, many family members w/ tumors, multiple tumors in individual
13
Q
HPV protein E6
A
- HPV is the most common cause of cervical cancer
- Viral protein E6 inhibits p53 by targeting for ubiquitination
14
Q
HPV protein E7
A
- HPV is the most common cause of cervical cancer
- Viral protein E7 inhibits p53 by targeting for ubiquitination
15
Q
Neurofibromatosis 1
A
- Characterized by cafe au lait spots i.e. multiple non-malignant peripheral nerve tumors
- Caused by a loss of function mutation of NF1 gene, which encodes for the protein, neurofibromin
16
Q
NF1 gene & neurofibromin: normal function
A
- NF1 encodes for the protein neurofibromin
- Neurofibromin accelerated GTP hydrolysis by Ras
- Lack of NF1 gene prolongs Ras signaling
