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.