Exam 3 - Cancer 2 Flashcards
1
Q
What are tumor supressor genes
A
- 2 types
- ) Proteins that normally restrict cell growth and proliferation
* inhibt progression through g1/S- ex: Rb and CKI
* Receptors or componets of a signaling pathways that inhibt proliferation
* promote apoptosis - Ex: Caspases
- ex: Rb and CKI
- ) Proteins that normally restrict cell growth and proliferation
- ) proteins that maintain the integrity of the genome
* check point control- ATM, ATR both detect DNA damage and stop cell cycle
* ATM***********TEST
* DNA Repair Enzyme of pathways
- ATM, ATR both detect DNA damage and stop cell cycle
- ) proteins that maintain the integrity of the genome
- If these tumor supressors genes are lost then cancer can occur
- requires 2 recessive mutations
*
- requires 2 recessive mutations
1
Q
A
2
Q
How is retinoblastoma and tumor suppressors related?
A
- inherited eye cancer in children
- Rb is a tumor supressor that inhibits progression into S phase
- Need to lose both gene Rb
- 2 forms
- 40% is familial where both eyes are affected
- 60% is sporadic (no family history) single tumor in one eye
- can occur in both tumor supressors (Rb) and oncogene (CKI)
- in the onco version
- CKI IS ABSENT so Cdk Cyclin is always active and will phosphorlate Rb to deactivate it and that allows proliferation to continue
- In regular version
- CKI is present to inhibit CDK from phosphorlatying Rb so that Rb cant stop progression into g1/S phase
- in the onco version
3
Q
What is the hereditary form of Retinalblastomia
A
- Family form (hereditary)
- loss of function or deletion of 1 copy of Rb in every cell
- predisposed to cancer
- 1 copy of Rb gene
- Eliminates one good copy and tumor forms
- loss heterozygosity (LOH)
4
Q
What is the sporadic form of Rb
A
- Non hereditary = start off with normal cells
- Two hit hypothesis
- first Rb gene obtains mutation then second mutation Rb
- Familial already has one mutation so they are predisposed to cancer
- Sporadic
- 2 normal Rb genes
- requires 2 mutations or “hits”
- MUCH More rare than hereditary form
*
- MUCH More rare than hereditary form
- requires 2 mutations or “hits”
- 2 normal Rb genes
5
Q
How are tumor suppressors inactivated or lost in Rb?
A
6
Q
What is P53?
A
- Huge tumor suppressor gene
- P53 is involved in
- Cell cycle arrest
- Dna Repair
- Apoptosis
- Block of angiogenesis
- P53 is VERY important because majority of cancers have p53 mutation
7
Q
WHat happens if you lose P53?
A
- Loss checkpoint control in cell cycle
- loss of cell cycle arrest in response to DNA damage
- loss of DNA repair activites
- Loss of apoptosis in response to DNA damage
- p53 is a gene regulatory protein
- Stimulates transcription of gene encoding CKI (cdk inHibitory protein) called P21
- P21 binds to g1/S-Cdk and S-Cdk and so will stop the cycle
- p53 also activates expression apoptotic proteins BH123 and Bh3
8
Q
What kind of factors(signals ) does p53 react to and what are the effects ?
A
- Reacts to:
- Hyperproliferative signals
- Dna Damage
- Telomere shortening
- hypoxia
- Causes :
- Cell cycle arrest
- senescence
- apoptosis
9
Q
What is a DNA tumor Viruses and an example of one?
A
- Pailloma viruses is the exampleand can cause warts and cervical cancer
- Viral DNA exists as extrachromosomal material (like plasmid in bacteria)
- Normally the replication of the viral DNA coincides with replication of chromomse
- however once viral DNA intergrates with host DNA it can interfere with the control of cell devision in basal cells and can cause a maignant tumor to develops
10
Q
WHat are the viral proteins of the papilloma virus ?
A
- The viral proteins that cause malignancy are E6 and E7
- These bind to 2 tumor suppressor genes Rb + p53
- CEels can replicate in an uncontrolled manner
11
Q
How does normal pathway and the viral pathway for proliferation of DNA tumor viruses compare?
A
- Normal
- Rb bound to E2F protein (gene regulatory protein) to inactivate transcription of cycllins and production of g1/s Cdk and S cdk does not happen
- p53 induces expression of p21 (a CKI) to prevent activity of CDK
- blocking proliferation
- VIral Protein
- E7 binds to Rb causes E2F to overexpress g1/S-CDK and S Cdk and cell grows and Divides
- E6 binds to p53 and inactivates it and so CKI (p21) is NOT produced
- Cell proliferation is activated by the virus
12
Q
How doe Onco genes and tumors compare?
A
- Overativity mutations: gain of function - ONCOGENES - involve single mutation event and activation of gene causing proliferation (dominant)
- Underactivity mutations: loss of function - TUMOR SUPPRESSORS GENES - involve genes that inhibt growth. Mutation event: one gene no effect; second mutation causes probelms (recessive)
13
Q
What is a proto-onco gene?
A
- Normal gene that is usually involved in refulation of cell proliferation that can be converted to cancer causing oncogene by mutation
- Transgenic mice are tools for tudying oncogene
14
Q
How does the Myc and Ras work as oncogenes sepeperatly and collectively?
A
- in MYC Tg, cell proliferation occurs but most cells do not give rise to cancer
- Ras Tg mouse tumors occurs as a more severe rate
- MYC Tg x Ras Tg mouse devlope tumors at a higher rate
16
Q
WHat are the barriers for cancer cell metastais ?
A
22
Q
WHat is hereditary nonpolyposis colorectal cancer (HPNCC) ?
A
- Cancers cells are unsual
- most HPNCC cells have normal chromosme number or near normal number of chromosmes
- Colorectal cancer cells usually have multiple copies of chromosomes
24
Q
What is the cause of chronic myelogenous leukemia?
A
- Translocation of 9 and 22 = phildelpha chromasome
- Bcr-Abl causes it
25
Q
What BCR-Abl (this post translocation )
A
- Abl is a tyrosine kinase for cell signaling
- N terminus BCR makes it hyperactive
- bth are fused during translocation
- BCR-ABl makes a highly active tyrosine kinase that highly xpressed
- causes cell proliferation = cancer CML
- treatment is GleevecL inhibts tyrosine kinase activity
- causes disappearance of phildelphia chromosome in >80% of patients
26
Q
A
