Download Cancer:19.3 A. - Oncogenes – cancer causing genes found in some

Cancer:19.3
A.
- Oncogenes – cancer causing genes found in some retroviruses and
counterparts found in Humans.
- Proto-oncogene – code for proteins that stimulate normal cell growth and
division.
- How do proto-oncogens become oncogenes? Fig. 19.11.
- A genetic change that leads to an increase in amount of the protooncogene’s product or activity of each protein molecule.
These genetic changes fall into 3 main categories:
- Transposable elements:
- if a translocated proto-oncogene ends up near an
overactive promotor its transcription may increase making it an oncogene.
- if a transposable element places a more active promotor
near a proto-oncogene then its expression increases.
- Amplification of proto-oncogenes:
- Increase in number of copies of proto-oncogene in cell.
- Point mutations in control element or proto-oncogene:
- Mutation in the control element leading to excess of
normal growth stimulating protein.
- Mutation within gene’s coding sequence resulting in
more active protein or resistance to degradation than normal protein.
ALL THESE LEAD TO CHANGES IN CELL CYCLE AND CELL ON PATH TO
MALIGNANCY. Ex. Colorectal cancer, breast cancer.
B.
- Tumor suppressor gene products normally inhibit cell division.
- Any decrease in normal activity can lead to uncontrolled cell growth.
- Some TS genes repair damaged DNA so that cancer-causing mutations
don’t build up.
- Some TS genes control adhesion of cells to each other or ECM.
- Some TS genes control cell anchorage (absent in cancer cells).
- Some TS genes are components of cell signaling pathways that inhibit the
cell cycle.
- Ex. 1.Ras protein is a G protein which relays signals from growth factor
receptor on plasma membrane to cascade of protein kinases.
-The end product is a protein that stimulates cell division Fig.
19.12a.
- Needs correct growth factor to be triggered.
- Mutation in ras gene can lead to hyperactive Ras protein that
triggers the kinase cascade in the absence of the growth factor leading to
excessive cell division.
- Ex. 2. p53 gene encodes transcription factor that promotes cell-cycle
inhibiting proteins.
- Signal is damage to DNA.
- Activator for several genes: p21 which halts cell cycle, genes that repair
DNA, suicide genes coding for proteins that cause apoptosis.
- p53 uses these ways to prevent cell form passing on mutations.
More than half a dozen somatic changes necessary for cell to become
cancerous, so as you get older mutations accumulate.
C. Malignant tumors:
- Invade other tissues.
- Accumulation of mutations that convert proto-oncogene to oncogene and
knock out tumor suppressor genes.
- Gene for telomerase activated which prevents shortening of ends so no
limit for cell division.
D.
- 5-10% of breast cancer is inherited. Of these mutations in BRCA 1 and
BRCA2 found in 50%.
- Mutation in one BRCA1 allele = 60% probability of cancer cf 2% if normal
alleles.
- Both genes are tumor suppressor genes (repair breaks in DNA strands).
- About 15% colorectal cancer associated with inherited mutations.
- Fig. 19.13 multi-step model for colorectal cancer.