The genes that have been implicated in
carcinogenesis are divided into two broad categories:tumor
suppressor genes(acting as cell’s brake) and Oncogenes (acting as
accelerators of cell proliferation)
Oncogenes are mutated forms of genes that cause normal cells to
grow out of control and become cancer cells. They are mutations of
certain normal genes of the cell called proto-oncogenes. In other
words, oncogenes are generally mutated forms of normal cellular
genes (proto-oncogenes).Oncogenes encode proteins that promote the
loss of growth control and conversion of a cell to malignant
state.
Proto-oncogenes are cellular genes that are expressed
during normal growth and developmental processes. A proto-oncogene is
a normal gene that can become an oncogene due to mutations or
increased expression. Proto-oncogenes code for proteins that help to
regulate cell growth and differentiation. Proto-oncogenes are often
involved in signal transduction and execution of mutagenic signals,
usually through their protein products. Some examples of proto-oncogenes
are RAS, WNT, MYC, ERK and TRK.
The proto-oncogene can become an oncogene by a
relatively small modification of its original function. The
activation of proto oncogenes by genetic alterations results in
altered levels of expression of the normal protein
Oncogenes are found in three forms:
1) Cellular proto-oncogenes that have been mutated.
2) Cellular proto-oncogenes that have been captured by
retroviruses, and
3) Virus-specific genes that behave like cellular proto-oncogenes
that have been mutated.
When a mutation event is involved, it is said that the
proto-oncogene has been "activated.” A mutation within a
proto-oncogene can cause a change in the protein structure, causing an
increase in protein (enzyme) activity and a loss of regulation .
Oncogenes are said to be "dominant" in their action. Since, they
promote cell growth and proliferation, their unregulated activity
would provide a continuous stimulation of cell division. Oncogenes can
be divided into the 5 different classes on the basis of function
1) Growth factors: These oncogenes
produce factors that stimulate cells to grow. The best known of
these is called sis (simian sarcoma virus). It leads to the
overproduction of a protein called platelet-derived growth factor,
which stimulates cells to grow.
2) Growth factor receptors: These are normally
turned "on" or "off" by growth factors. When they are "on," they
stimulate the cell to grow. The best-known examples of growth
factor receptor gene amplification are erb B and erb B-2. Both of
these oncogenes are targets of newly developed anti-cancer
treatments.
3) Signal transducers: These are the intermediate pathways between
the growth factor receptor and the cell nucleus where the signal
is received. Like growth factor receptors, these can be turned on
or off. When they are abnormal in cancer cells, they are turned
on. Two well-known signal transducers are abl and ras.
4) Transcription factors: These are the final
molecules in the chain that tell the cell to divide. These molecules
act on the DNA and control which genes are active in producing RNA and
protein. The best known of these is called myc.
5) Programmed cell death (apoptosis) regulators: These
molecules prevent a cell from committing suicide when it becomes
abnormal. When these genes are overactive they prevent the cell from
going through the suicide process. This leads to an overgrowth of
abnormal cells, which can then become cancerous. The most well
described one is called bcl-2.
Mutations in microRNAs can lead to activation of oncogenes. New
research indicates that small RNAs 21-25 nucleotides in length called
microRNAs (miRNAs) can control expression of these genes by down
regulating them. miRNA expression levels have diagnostic and
prognostic implications, and their roles as anticancer therapeutic
agents is promising and currently under investigation
