Molecular Genetics of Prostate Cancer
Molecular genetics is a powerful tool which enables investigators
to understand the basis for cancer. Dr. William Isaacs has made
some extraordinary observations on defects in molecular mechanisms
that may be responsible for the development of prostate cancer.
There are a variety of proteins that act like glue holding normal
cells together. When these adhesion molecules disappear, prostate
cells become disorganized and are less able to carry out their normal
activities. This also makes them better able to grow, to move around,
and to invade surrounding tissues and vessels. Dr. Isaacs is
investigating two protein adhesion systems (_ catenin and E-cadherin).
When these adhesion molecules are absent, prostate cancer cells act
more aggressively. In an experimental setting he has been able to
restore this adhesion system to cancer cells that are deficient
and in this process block their ability to form tumors. The
identification of this deficiency in prostate cancer cells may
be a useful marker for identifying cancers that are highly aggressive.
In another line of experiments, he has identified a relatively small
area on chromosome 8 that is consistently deleted when prostate
cells become cancerous. This region is likely to contain a gene
that normally plays a role in preventing the uncontrolled growth
of prostate canccr cells. The identification and characterization
of this gene should provide important insight into the critical,
perhaps initial steps, in the formation of prostate cancers.
- Bova, G.S., Carter, B.S., Bussemakers, M.J.G., E.
Mitsuru, Fujiwara, Y, Kyprianou, N., Jacobs, S.C., Robinson,
J.C., Epstein, J.1., Walsh, P.C. and Isaacs, W. B.:
Homozygous deletion and frequent allelic loss of chromosome
8p22 Loci in human prostate cancer. Cancer Res. 53:3869-3873, 1993.