Cancer Flashcards
(33 cards)
What causes cancer?
somatic mutations that deregulate the signaling pathways that control these processes
oncogenes
dominantly acting gene that can contribute to cancer; dominant, drive cell growth or survival, accelerator stuck to the floor
tumor suppressor genes
genes that must lose their function to become tumorgenic: recessive, normally inhibit cell growth or survival, brake fails
gate keepers (tumor suppressors)
recessive, preserve genomic integrity
differences between normal and tumor cells (5)
- contact inhibition 2. serum requirements 3. anchorage independent growth 4.tumorigenesis in mice 5. morphology
proto-oncogenes
a normal gene that can become an oncogene through mutation
Mutations that convert proto-oncogenes to oncogenes
- create over-expression of a normal protein 2. create abnormal, constitutively active protein
acutely transforming retroviruses
defective viruses that have picked up an oncogene and express it in a cell
slow transforming retroviruses
replication competent viruses that activate a cellular proto-oncogene through inserting adjacent to it and changing its expression
Ex. Growth factor oncogene: v-sis oncogene
overexpresses PDGF B (growth factor) - generates its own growth factor so that it can be turned on all the time(autocrine or paracrine)
Ex. Growth factor receptor oncogenes: EGF receptor and Her2 (v-erbB)
mutation truncates the protein that dimerizes (v-erbB) and will activate tyrosine kinase (no growth factor needed)
Ex. Intracellular signal transducer oncogenes: 1. Ras 2. v-RAF
- if GAP affected so that it cannot convert RasGTP to RasGDP, Ras will stay on 2. v-RAF constitutively activates pathway
Ex. Of nuclear transcription factor oncogenes: MAP Kinase
may over phosphorylate and over-activate ets family transcription factors and subsequently fos
Ex. Of cyclin oncogene: vin1 (cyclinD)
vin1 will push cells through the G1/S transistion of the cell cycle by phosphorylating Rb and inactivating it so that the cell cycle can procede
Ex. Anti-apoptosis pathway oncogene: Bcl-2
when overexpressed, the cell cannot release cytochrome C from the mitochondria, so it can’t undergo the apoptotic process
inherited retinoblastoma
early onset, multiple tumors, bilateral
sporadic retinoblastoma
late onset, one tumor, unilateral
inheritance pattern of retinoblastoma
need two “hits” to have the tumor (inherited already has one hit in all cells, more likely to get the second hit somatically)
retinoblastoma
- caused by mutations that inactivate both Rb alleles (recessise at the cell level) 2. genetically it is inherited in a dominant way (bc it is so likely that they will acquire a second somatic mutation (90% likelihood))
loss of heterozygosity (LOH)
when in tumor suppressor genes, the cell is heterozygous for the allele in normal cells - but in tumor cells there is a missegregation, gene conversion, or independent mutation event that makes the cell homozygous for that allele (only have mutant allele)
Types of Tumor Supressors: cell cycle inhibitor proteins - p16
p16 regulated G1/S, without it, the cell will go through the cell cycle without this regulating step
Types of Tumor Supressors: signaling pathway proteins - TGFB Pathway
pathway that activate genes that regulate the cell cycle, if you can’t activate the pathway there will be unregulated proliferation bc none of the genes have been expressed
Types of Tumor Supressors: inhibitors of cell proliferation pathways, Wnt (also GAP-NF1)
Wnt regulates balance of cell death vs cell growth (esp in intestine). Need Wnt to activate transcription of cell cyclin (cyclin D) to promote cell growth
Wnt pathway tumor suppressors
APC, Axin
