The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 42

In normal organisms, cell proliferation is balanced by regulated cell loss
through apoptosis. Many tumour suppressor genes are involved in cell pro-
liferation, genetic stability, and cell death, and they often show mutation in
cancer. Such mutations in these genes generally ablate the ability to cause
apoptosis and result in increased cell numbers.
The normal function of tumour suppressor genes is to control cell pro-
liferation. The two best understood tumour suppressor genes are the reti-
noblastoma ( RB1 ) gene and the TP53 (also called P53 ). Retinoblastoma
provides the classical model for a recessive tumour suppressor gene in
that both paternal and maternal copies of RB1 must be inactivated for the
tumour to develop. For TP53 and some other tumour suppressor genes,
mutation at one allele may be sufficient to give rise to the altered cell
phenotype [56-60].
Possible Functions of Tumour Suppressor Genes
The following are some possible functions of tumour suppressor genes:
1. Direct reversal of oncogene action: In order to reverse the action of
oncogenes, some tumour suppressor genes introduce more copies of
the normal gene into the cell.
2. Genes that encode growth inhibitors: Most of the oncogenes act by
inducing cell proliferation at the wrong time and place. A set of fac-
tors that inhibit cell growth can work against this action of tumour
producing genes. Some examples of proteins with inhibitory prop-
erties are the interferons, tumour growth factor-β, and the tumour
necrosis factor [62].
3. Cell-cell interaction: Several investigators have proposed that this
action of some normal-cell products and drugs is correlated with
presence of gap junctions, through which the cell-cell contact is
achieved.
4. Tumour angiogenesis factor: Angiogenesis is the process by which
a vascular network of blood vessels develops, and its importance
in tumourigenesis has been recognized. Tumour angiogenesis fac-
tor (TAF), a substance synthesized and secreted by tumour cells, is
essential for their survival. Some genes encode a few cell products
that interfere with the action of TAFs.
5. Suppression by terminal differentiation: Cells that have undergone
terminal differentiation no longer divide and thus cannot give rise
to tumours. One mode of suppression, therefore, consists of dividing
partially differentiated cells into the terminal state.