ANDROGEN RECEPTORS IN CANCEROUS PROSTATIC TISSUE

  • Tindall, Donald J, (PI)

Project: Research project

Project Details

Description

Cancer of the prostate is the second most common cancer in men and the
third leading cancer killer. The etiology of the disease is unknown;
however, it is absent in castrated individuals, and many tumors retain the
property of androgen dependence similar to normal differentiated prostate
tissue. It is clear that the greatest progress in understanding steroid
hormone action in tumors is through understanding better the properties and
physiology of specific steroid receptor proteins. Therefore, there is a
need for a more reliable and specific means for studying androgen receptors
in tumor tissue. An antibody to the receptor molecule would provide a
useful probe for studying the androgen receptor properties in cancer tissue. During the last granting period, we developed the necessary techniques for
purifying the androgen receptor from Dunning prostatic tumor. These
techniques included both differential binding to DNA-Sepharose and
testosterone-affinity chromatography. Furthermore, we characterized the
receptor with respect to a number of its physicochemical and
steroid-binding properties. We demonstrated three forms of the receptor:
a 9.1S nontransformed receptor which does not bind to DNA, a 7.7S
receptor-ribonucleoprotein complex and a 4.4S transformed receptor which
binds to DNA. The 4.4S receptor appears to be a 120,000 dalton monomer
which binds both androgenic steroids and polynucleotides. The other forms
of the receptor appear to be composed of the monomer together with other
receptor-associated proteins or ribonucleoproteins. In the current
proposal we plan to purify each of these receptor species and develop
monoclonal antibodies to both the monomer subunit and the
receptor-associated proteins. By using these antibodies, we will 1) map
out the steroid- and nucleotide-binding domains on the receptor monomer
with respect to the N-terminal amino acid, 2) characterize the putative
nonsteroid binding proteins associated with the 9.1S receptor, 3)
characterize the ribonucleoprotein associated with the 7.7S receptor and 4)
determine if these receptor-associated proteins play any physiological role
in regulating androgen receptors in target tissues. Antibody probes to the
androgen receptor will allow further physicochemical characterization of
the protein in androgen regulated prostatic cancer tissues. The long range
objective of our laboratory is to be able to use these antibodies to
quantitate androgen receptors and determine their mechanism of androgen
action in cancerous prostate. This would be a new diagnostic tool for
evaluating potential treatment protocols in arresting this disease.
StatusFinished
Effective start/end date8/1/823/31/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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