Flashcards in Molecular background of tumorigenesis. Deck (15)
Difference between just immortalized cells and transformed cells
can replicate indefinitely, but don't metastasize within the animal,
Still only grow in a monolayer and need attachment, still subjected to contact inhibition
Immortalized and also are not subject to attachment or contact inhibition,
will proliferate while floating and in the absence of growth facto
induced by telomere shortening
tumor suppressor factors
multiple mechanisms how p53 inhibits tumors
Causes cell cycle arrest and senescence
Initiates DNA repair pathways
DNA viruses that can inhibit p53
HPV E6 inhibits p53
E7 inhibits Rb
Adenoviruses inhibit p53 and Rb
SV40, simian vacuolating virus 40, a polyoma virus, other polyoma viruses also inhibit p53 and Rb
How does Rb inhibit proliferation?
Binds to E2F transcription factors (a family of TFs), preventing them from activating cell cycle genes.
What are the proteins that specifically inhibit p53 from those viruses?
E6 from HPV
What do the adenoviral proteins E1A and E1B inhibit?
E1A inhibits RB
E1B inhibits P53
what are 3 ways tumor cells bypass senescense
What RNA viruses are tumorviruses?
Retroviruses, by integration of oncogenes into genome.
Rous Sarcoma Virus
What is the oncogene in Rous Sarcoma Virus
v-src, which is a mutated version of the somatic c-src non-receptor tyrosine kinase. c-src is a normal host proto-oncogene.
induces motility, proliferation, survival.
What kind of proteins are coded by human proto-oncogenes?
Tyr Kinase receptors
Intracellular signaling proteins,
non-receptro tyroskine kinases
Nuclear TF receptors,
Positive cell cycle regulators, cyclins
Inhibitors of Apoptosis, BCL2
How do protooncogenes become oncogenes
By activating mutations, basically list any way a mutation can increase gene activity.
Chormosomal translocation, different regulation, increased expression
Deletions or repressor regions
Insertion of a viral DNA hyperactive promoter region in front of the gene.
How can Ras be permanently activated via mutation
A point mutation that changes Gly -> Val
Ablates its GTPase activity, thus it binds GTP becoming active and then never cleaves it to GDP to inactivate itself.
Human tumor viruses
HPV many strains
Kaposi sarcoma virus
Merkel cell polyomavirus