Mutations of Receptor for Androgens
Androgens are the major hormones that stimulate the prostate to grow.
Their action in the cell is mediated by a specific protein called a receptor.
When androgens enter the prostatic cell, they bind to this receptor,
like a key in a lock, and this steroid -receptor complex
activates celluar growth and function. Thus, androgen receptors
are very important for hormone action.
Dr. Evelyn Barrack has recently demonstrated that as prostate
cancer progresses, the receptor for androgens may undergo mutations.
Recently, Dr. Schoenberg and Dr. Barrack have demonstrated that a
specific mutation in the receptor is associated with a paradoxical
response to hormones. Flutamide is an antiandrogen that blocks the
binding of androgens to the receptor. It is frequently used in
combination with castration or treatment with an LHRH agonist.
Some people believe that flutamide may be useful in providing
total androgen ablation. However, in some patients flutamide
actually stimulates cancer growth and PSA levels paradoxically
fall when flutamide is discontinued. They demonstrated that
in one patient who had this paradoxical stimulation by flutamide,
there was a mutation in the androgen receptor. Further elucidation
of androgen receptor mechanisms may make it possible to improve
hormonal therapy for prostate cancer.
- Schoenberg, M.P., Hakimi, J.M., Wang, S., Bova.
G.S., Epstein, J.1., Fishbeck, K.H., Isaacs, W.B., Walsh, P.C.
& Barrack, E.R.: Microsatellite mutation (CAG24-18)
in the androgen receptor gene in human prostate cancer. BBRC