oncogene Flashcards
What is oncogenes
gain of function (stuck accelerator)
cell growth and antigrowth signals are always there but if the pro growth signals are stuck then it will always send out the signal
a dominant phenotype
What is an oncogenic mutation?
a gain of function of a gene associated with cancer progression
a gain of function that causes cancer
What is proto-oncogenes and how do they relate to oncogenes?
promote normal cell divison
mutant forms of proto-oncogenes induce or continue uncontrolled cell division
What type of phenotype is oncogenes
dominant mutations
they only require one allele mutation to result in an altered phenotype
what are oncogenic mutations?
5 mechanisms
- point mutation
- gene amplification
- chromosomal translocation
- local DNA rearrangements
- insertional mutagenesis
What is the effect of point mutations on oncogenic proteins?
abnromal (hyperactive) protein (RAS)
What is the effect of gene amplification on oncogenic proteins?
excess normal proteins (MYC)
What is the effect of chromosomal translocation on oncogenic proteins?
excess normal protein or abnormal (hyperactive) protein (BCR-ABL)
What is the effect of local DNA rearrangements on oncogenic proteins?
insertion or deletion or inversion or transposition all create abnormal (hyperactive) proteins
What is the effect of insertional mutagenesis on oncogenic proteins?
excess normal protein
What do oncogenic RAS do?
they increase RAS activity and increase in proliferation
what is the steps of RAS pathway
- EGF (growth factor) binds to the EGFR (growth factor receptor) and then TK receptors dimerize and recruit phosphates
- phosphates recruit GRB2 and connect through SH2 domain
- GRB2 recruits SOS and connects through SH3 domain
- SOS is a GEF that turns GDP into GTP which helps activate RAS pathway
(then farnesyl transferase must be added to fully activate RAS)
how is RAS activated? what does it have that the inactived doesnt?
RAS GDP = inactive
RAS GTP = active
RAS GTP + farnesyl transferase = fully activated
what are the types of RAS and the cancer associated with it?
HRAS
NRAS
KRAS: G12C – lung (NSCLC)
G12D – pancreatic, colorectal
what is a common cancer for BCR-ABL?
CML