Oncology Flashcards
MYC (tie to cancer)
a TF from chromosome 8,
RAPIDLY activated to promote cell division, & modulates telomerase.
*over-expressed in many tumors, esp. Burkitt’s Lymphoma
oncogenes (examples)
genes that are activated (from proto-oncogenes) to promote unregulated growth => cancer
Ex: TGF-a, EGFR, Ras, MYC, Cyclins
Tyrosine kinase
enzyme that phosphorylates protein tyrosine residues, important for intracellular signalling.
mutations in:
Bcr-Abl => CML (constitutively active)
Jak2 => polycythemia vera (loss of inhibition)
RAS (tie to cancer)
oncogenic signal transduction protein,
- stimulates MAP-kinase pathway (via Raf)
- auto-inactivation (by binding Gap)
* point muts in RAS = #1 mut in cancers => uncontrolled prolif.
p53
tumor suppressor gene, #1 target of cancer chemoTx!
= G1-S checkpoint, to keep cells from progressing if damaged DNA
* loss of function –> mutated (cancer cells) progress past checkpoint
proteins in Intrinsic Apoptosis
Pro-apoptotic: Bax & Bak => increase mitochondrial membrane permeability -> release cytochrome C
Anti-apoptotic: Bcl-2 & Bcl-xl => inhibit bax & bak
*over-expression of Bcl-2 -> Follicular B cell lymphoma! t(14,18)
DNA repair mechanisms & assoc. cancers
- Mismatch Repair: single base mismatches => HNPCC
- Nucleotide Base Excision Repair: correct bulky lesions (disrupted helical architecture) => Xeroderma pigmentosa
- Double Strand Break Repair: cut out cross-links
=> Fanconi anemia, Ataxia telangectasia, Bloom syndrome
Initiators
agents that cause DNA DAMAGE, but not enough to induce cancer alone.
(exposure to initiators 1st, then promoters => cancer)
ie: chemicals, radiation, oncogenic viruses
Promoters
agents that INDUCE CANCER in already initiated/altered cells
* only cause cancer IF pre-existing DNA damage.
(must occur after exposure to initiator)
ie: hormones, drugs, phenols