Abnormal Signalling and Cancer
Mutational Routes to Cancer
– Two Primary Routes:
(1) hyperactivate stimulatory gene
dominant effect
altered gene called oncogene
(2) inactivate inhibitory gene
missing gene called tumor suppressor gene
Retroviruses
– not important cause of human cancer, but have been shown to cause cancer in laboratory animals
injects RNA into host, reverse transcription gives DNA, DNA incorporated into host genome
can cause cancer in two ways:
(1) virus may carry oncogene
origin probably from mutated proto-oncogene picked up from a previous host
many viral oncogenes are similar in structure to proto-oncogenes in humans
(2) virus can also insert in such a way as to activate a host proto-oncogene
cause alteration or truncation of gene sequence
insert next to promoter to cause hyperactivation or inappropriate expression
Oncogenes
– proto-ongogenes are converted to oncogenes
single gene may have different mutations that cause different types of cancer
usually takes more than one mutation to cause cancer
some transgenic mice contain mutation in all DNA but only cancerous in some tissues
i.e., if one mutation is corrected for or compensated by another gene, need to knock out both genes in order to get a cancer
mice with more than one mutation have higher incidence of cancer
protooncogenes code for stuff important in regulation of growth, division and death, usually by means of signaling message from other cells
RTK growth receptors
G-Proteins
growth factors
nuclear proteins
cytoplasm-located kinases
steroid receptors
different types of mutation
deletion, point mutation, insertion, rearrangement
in gene: hyperactive product
in promoter region: hyperactive expression (gene amplification)
amplified to high copy number from improper replication