Cancer II Flashcards
What are the two major categories of tumor suppressor genes?
Proteins that normally restrict cell growth and proliferation
Proteins that maintain integrity of the genome
What are some tumor suppressor proteins that normally restrict cell growth and proliferation
Intracellular proteins that inhibit progression through G1 in the cell cycle (Rb, CKI)
Receptors or components of a signaling pathway that inhibit cell proliferation
Proteins that promote apoptosis
What are some tumor suppressor proteins that maintain integrity of the genome?
Checkpoint control proteins (ATM, ATR-detect DNA damage - stops cell cycle) - Ataxia Telangiectasia
DNA repair enzymes or pathways
What is retinoblastoma?
Inherited eye cancer in children. rare and occurs before age 2
Diagnosed before age 5
Involves Rb - a tumor suppressor that inhibits cell division
What are the two forms of retinoblastoma?
Hereditary (40%-both eyes) and sporadic form(60%-one eye)
Describe hereditary form Rb
Loss of function or deletion of one copy of Rb in every cell
Somatic event occurs and eliminates one good copy and tumor forms. thus a loss of heterozygosity
Describe sporadic form Rb
non-hereditary
two hit hypothesis- first Rb gene obtains mutation then needs second mutation Rb
More rare than hereditary form
What are proto-oncogenes?
Normal gene, usually involved in regulation of cell proliferation that can be converted to a cancer-causing oncogene by a mutation (overactivity mutations)
What are the four functions of cancer genes?
Regulate cell proliferation
Control cell growth
Control division
Control apoptosis
Cdk or cyclin:
A proto-oncogene or a tumor suppressor gene?
Proto-oncogene
Active CKI stops Cdk
Rb binds E2F
CKI or Rb:
A proto-oncogene or a tumor suppressor gene?
Tumor suppressor gene
CKI absent so Cdk always active
Rb inactive and E2F drives S-Cdk activation by making more cyclins
What is the guardian of the genome?
p53: huge tumor suppressor gene Involved in: Cell cycle arrest DNA repair Apoptosis Block of angiogenesis
If you lose p53, what functions will be lost?
- loss of checkpoint control in cell cycle
- loss of cell cycle arrest in response to DNA damage
- loss of apoptosis in response to DNA damage
- loss of DNA repair activities
How is p53 associated with p21 and pro-apoptotic proteins?
p53 upregulates p21
p53 activates expression of pro-apoptotic proteins
Bcl2:
proto-oncogene or tumor suppressor?
proto-oncogene