Oncogenes, Cell Growth, and Cancer (2) Flashcards
What are the oncogene transformation mechanisms?
Translocation
Amplification
Point mutation in control element
Point mutation in gene
Give an example of a growth factor gene as an oncogene
Sis oncogene
From Simian sarcoma virus
Encodes PDGF-like growth factor
Stimulates cell proliferation - causes hyperplasia
Give an example of a deletion in a growth factor receptor gene forming an oncogene
v-erbB
Mutant EGF tyrosine kinase receptor without ligand-binding domain or autoinhibitory region
Signals to nucleus without EGF binding - stimulates cell proliferation
What forms the autoinhibitory region of a tyrosine kinase receptor?
22AA sequence - at C-terminus
Give an example of a point mutation in a growth factor receptor gene forming an oncogene
Mutation in EGF receptor transmembrane domain - changes conformation - dimerisation without ligand - activation
Give an example of overexpression of a growth factor receptor gene forming an oncogene
c-erbB2
Overexpressed in some breast cancer cases
Causes tumour growth
Which proteins are activated by EGFR activation?
SRC, PI3K, Ras, PLC
Give an example of a DNA re-arrangement in a growth factor receptor gene forming an oncogene
HGFR (c-Met)
Causes cluster of cancer cells to scatter
Onc-Met mutation has cytosolic domain fused to another protein - activated - overexpression in tumours
What is HGF usually produced by?
Fibroblasts in basal membrane (epithelial monolayer) over vessels
What is the effect of an HGF mutation on epithelial cells?
Produce growth factors themselves
Grow on top of each other
Produce proteases - penetrate basal membrane - move into blood - obtain O2 and nutrients - move around body
How does HGF mediate cell motility and cell survival?
Via PI3K
How does HGF mediate cell proliferation?
Via MAPK
What is the Philadelphia chromosome translocation?
From chromosome 9 to 22
Fusion product is oncogene
What type of molecules are Rac1 and RhoA?
Small GTPases
What do Rac1 and RhoA control?
Tight cell-cell junctions
