L04 - Oncogenes Flashcards
What are the two types of retroviruses and how do they work?
There are slowly transforming retroviruses that cause tumours after many months because they integrate into the dna and deregulate cellular oncogenes.
Acutely transforming retroviruses cause tumours rapidly due to viral oncogenes carried by the virus which resemble the host cellular genes.
What is the lifecycle of a retrovirus?
The retrovirus inserts its genome into the host cell. reverse transcriptase is used to make a copy of the viral RNA then helicase is used to open the host dna and insert the RNA. This can now be transcribed and translated to make new viruses.
A series of experiements on chickens concluded that viral oncogenes looked very similar to host cell genes, what else was deduced from this?
That the cell is being supplied growth factors by an autocrine loop from itself. Normally works by paracrine but in cells with the viral oncogene they are producing growth factors for themselves.
Do human cancers involve retroviruses?
With 1 or 2 exceptions most human cancers do not involve retroviruses.
What are the two main causes of increased c-myc expression?
Chromosomal translocation in Burkitt’s lymphoma upregulates c-myc
ALV provirus inserting close to c-myc
What does overproduction of c-myc lead to?
It causes upregulation of protooncogenes
What are the two ways the cellular protooncogenes are altered?
Change in the function of an encoded oncoprotein
Change in expression of an oncogene
What can lead to a change in function of oncoproteins?
Point mutations at a specific site
Chromosomal abnormalities
What are the two main ways that RTKs are effected in cancer?
amino acid changes or deletions - leads to growth factor independent signalling
Gene overexpression- leads to growth factors having a larger effect on the RTK
What is typically the cause of dereguated ras signalling?
The GTPase activity is reduced so this means that there is less conversion of ras back to the gdp inactive form.
What does deregulated ras signalling lead to?
Uncontrolled transcription of growth promoting genes
What translocation typically occurs in BCR-Abl signalling?
In some patients, a translocation occurs between ch22 and ch9
Ch 22 breakpoint within BCR gene
Ch 9 breakpoint within Abl gene
What is the result of BCR-Abl signalling?
Leads to constantly activated tyrosine kinase which causes mitogenic signalling independent of growth factors
