Oncogene Function

Importance of proto-oncogenes in the cell -> Evolutionary

conservation.
They are genes that can promote in cell growth ; specific
transcript-ion factors or components of growth stimulating signal
pathways.
Eg->c-src in vertebrates and c-ras in yeasts and human
beings.
In normal cells -> low levels present
In transformed cells -> high levels present

Oncogene products
The known products of oncogenes are proteins that can
be classified broadly in
The following four categories :
O-

Tyrosine kinases

O-

growth factors

O-

Gtp-binding proteins

O-

Dna-binding proteins

Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP
to a protein in a cell. It functions as an "on" or "off" switch in many cellular
functions. Tyrosine kinases are a subclass of protein kinase.
The phosphate group is attached to the amino acid tyrosine on the protein.
Tyrosine kinases are a subgroup of the larger class of protein kinases that
attach phosphate groups to other amino acids (serine and threonine).
Phosphorylation of proteins by kinases is an important mechanism in
communicating signals within a cell (signal transduction) and regulating
cellular activity, such as cell division.
Protein kinases can become mutated, stuck in the "on" position, and cause
unregulated growth of the cell, which is a necessary step for the development
of cancer. Therefore, kinase inhibitors, such as imatinib, are often effective
cancer treatments.
Most tyrosine kinases have an associated protein tyrosine phosphatase,

Gtp-binding proteins can send continuous or

amplified signals across membranes to
specific cells and cause abrupt growth.
V-myc is a gene product protein that binds to
DNA
many transcription factors can signal
innappropriate transcription , also inducing
transformation

Clonal evolution
Conversion of healthy cell into a cancerous one can involve
many steps
These include a normal mass of cell to go through hyperplasia
to dysplasia to eventually cancer ( invasion of neighbouring
tissues
and metastasis.
Steps involved in colorectal cancer familial adenomatous
polyposis
1)The APC gene mutates in a normal cell causing a condition called
aberrant cryptic foci. Exact role of APC protein is unknown. It binds
to Beta-catenin(involved in cell adhesion) and activates D1
promoter cellular proliferation.
Thus mutation of APC accumulation of catenin cell cycle

The next genetic change results in an early adenoma(benign growth)

Intermediate adenoma mutation of the ras oncogene autonomous
growth signals
by the Ras GTP-binding protein.
Late adenoma mutation of deleted in colorectal cancer gene or DPC4
or JV18
Mutationloss of p53 protein full blown cancer.
Throughout FAP a cell sequentially follows all these mutations to turn
cancerous
(clonal evolution).
Cancerous cell have much greater mutation rates than normal cells. Eg
mutations in
p53 causes higher mutation rates in the cell.

Traits of cancerous cells

1.) they provide their own growth
signals and ignore inhibitory signals
(potentially
Limitless growth)
2.)They avoid apoptosis.
3.)they create new blood supplies
angiogenesis new blood vessels grow
in the tumor cells .
4.)they are capable of invasive growth
and metastasis.