Cancer 2 Flashcards
(28 cards)
What is a proto-oncogene?
A normal gene that regulates cell growth and division; it can become an oncogene if altered.
What is an oncogene?
A mutated or overexpressed proto-oncogene that promotes uncontrolled cell division and contributes to cancer.
How many alleles of a proto-oncogene need to be altered for oncogenic activity?
Only one allele—oncogenes act in a dominant fashion.
What are three mechanisms that convert proto-oncogenes to oncogenes?
- Overexpression of a normal protein
- mutations
- viral copy
How can viruses contribute to oncogene activation?
By inserting viral copies (homologue only) of proto-oncogenes into the host genome that suit viral replication
how can mutations convert proto-oncogenes into oncogenes?
through point mutations producing an overactive protein
through chromosomal translocation fusing abnormal parts of the protein together
how can overexpression of a normal protein be oncogenic?
gene amplification due to multiple copies of the gene due to abnormal DNA replication
over-active promoter due to chromosomal translocation
how can chromosomal translocation alter proto-oncogenes into oncogenes?
by fusing abnormal parts of proteins together and by causing a region of a proto-oncogene to become oncogenic due to chromosomal translocation
describe normal GF stimulation of the cell cycle
growth factor binds to a receptor tyrosine kinase, which induces transphosphorylation of the tyrosine kinase domains, which causes signal transduction within the cell to trigger changes in gene expression which leads to cell cycle
- in the G1 phase of the cell cycle, CYCLIN D binds CDK4/6 and this gets to the R point where cell will begin division
what does PDGF-B normally do?
made mesenchymal cells grow during wound healing
what is v-sis and how does it work?
It is a viral homologue of PDGF-B that mimics host growth signals
- only one gene is required to drive cell proliferation
what is the CAUSE and RESULT of a cancer cell overproducing PDGF-B?
mutation in a proto-oncogene causes an increase in PDGF-B production in the cell, which increases cell proliferation which drives cancer aka tumorigenesis
What receptor family is commonly mutated in cancer to cause ligand-independent signalling?
EGFR (Epidermal Growth Factor Receptor) family
how does the EGF-R contribute to oncogenic signalling?
a deletion mutation of HER1, or a val-gln mutation in HER2 causes a loss of the extracellular domain, and the intracellular domains spontaneously dimerise in the abscence of a growth factor.
which protein does a deletion mutation in HER1 give?
the ErbB oncoprotein
- it was found in an erythoblastosis virus
which protein does a val-gln mutation in HER2 give?
Neu oncoprotein
- it was discovered in Neuroblastoma
the Neu oncoprotein and the ErbB oncoprotein are called what?
ligand-independent receptor oncoproteins
proto oncogene receptor proteins become __________-________ _______ ________ through ____________ ________
ligand-independent receptor oncoproteins, oncogenic mutations
What does Ras normally do in the cell?
Ras transduces signals through GEFs (guanine nucleotide exchange factors) such as SOS, which replace their GDP with GTP, allowing Ras continue that signal to downstream effectors like Raf, controlling cell growth
What role does GAP play in Ras signalling?
GAP inactivates Ras by inducing Ras to hydrolyse GTP to GDP
What effect do point mutations in Ras GTP/GDP binding site have?
They prevent GAP-mediated inactivation, locking RAS in its active GTP-bound form
What percentage of pancreatic cancers carry a K-RAS mutation?
90%
Why is RAS signalling described as “constitutive” in cancer?
Because RAS remains permanently active regardless of upstream signals.
- stopping SOS GDP-GTP doesn’t effect mutated Ras
What does “dominant trait” mean in the context of oncogenes?
The presence of a single oncogene allele is enough to alter cell behaviour.
