Lecture 29: Cancer 2 Flashcards
(49 cards)
What type of proteins are usually encoded by tumor suppressor genes?
Proteins that inhibit cell proliferation
What are the 2 major categories of proteins that tumor suppressor genes encode?
Proteins that normally restrict cell growth and proliferation
Proteins that maintain integrity of the genome
What are examples of proteins that normally restrict cell growth and proliferation?
Rb, CKI, proteins that promote apoptosis (caspases)
What are examples of proteins that maintain the integrity of the genome?
ATM, ATR (checkpoint control - detect DNA damage), DNA repair enzymes or pathways
What type of gene is Rb?
A tumor suppressor - it prevents over-proliferation of cells and inhibits cell division
What are the 2 forms of retinoblastoma?
Hereditary
Sporadic
Are the majority of Retinoblastoma cases hereditary or sporadic?
Sporadic = 60%
What is the difference between hereditary and sporadic retinoblastoma?
Hereditary = familial, BOTH eyes are affected
Sporadic = NO family history, single tumor in one eye
Which type of retinoblastoma is associated with a loss of heterozygosity?
Hereditary
What leads to the loss of heterozygosity?
Person initially starts one Rb deletion in every cell (inherited), then somatic event occurs and eliminates the one good copy –> tumor forms
In the sporadic form of Rb, you start off with all normal cells - no mutations of Rb. What hypothesis describes the development of Retinoblastoma in this case?
Two-hit hypothesis - first Rb gene obtains mutation, then another mutation must occur to develop Retinoblastoma
What binds to the promoters of G1/S cyclin and S cyclin genes to drive the cell cycle and what is the effect of the Rb protein on this interaction?
E2F - this is inhibited by interaction with the Rb protein, so Rb inhibits cell division
When Rb is mutated, cell division proceeds uncontrolled –> cancer
True or false: The Rb pathway includes tumor suppressor genes only, not oncogenes
False – the Rb pathway can include both tumor suppressor genes and oncogenes
What is the action of an active CKI (p16)?
Inhibits Cdk, so Cdk-cyclin complex will not phosphorylate Rb
Rb then binds E2F and blocks it, inhibiting cell proliferation
What is the action of Cdk-cyclin in the absence of a CKI?
Cdk will remain permanently active, Cdk-cyclin complex can now phosphorylate Rb
Rb will be inactive and E2F will drive S-Cdk activation by making more cyclins
What type of gene are Cdks or cyclins considered when they are overproduced, why?
Oncogenes - bc overproduction can overcome the amount of CKIs and lead to uncontrolled growth –> cancer
What type of genes are CKI and Rb considered, why?
Tumor suppressor genes, because if these are lost, there is no control of Cdk-cycling or suppression of entry into the cell cycle –> cancer
What tumor suppressor gene is considered the guardian of the genomic galaxy because it is mutated in the majority of cancers
p53
What are the 4 processes that p53 is primarily involved in?
- Cell cycle arrest
- DNA repair
- Apoptosis
- Block of angiogenesis
If you lose p53, what functions are you losing?
- Loss of checkpoint control in cell cycle
- Loss of cell cycle arrest d/t DNA damage
- Loss of DNA repair
- Loss of apoptosis d/t DNA damage
What are the 2 functions of p53 as a gene regulatory protein?
Stimulates transcription of gene encoding CKI called p21
Activates expression of pro-apoptotic proteins BH123 and BH-3
What 2 conditions are caused by papilloma viruses?
Warts and cervical cancer
How does viral DNA exist in human cells after infection with the virus?
Extrachromosomal material - like a plasmid
What occurs if viral DNA integrates into host DNA in terms of tumor development?
Viral DNA will interfere with control of cell division in basal cells –> malignant tumor development
