Characterization of androgen receptors in normal and malignant human prostatic tissues

Abstract

The aim of this work was to study the physico-chemical characteristics of androgen receptors of normal and malignant human prostatic tissues. Association (k+1) and dissociation (k-1) rate constants and sedimentation profiles on sucrose density gradients were determined on [3H]androgen receptor complexes. In the presence of 20 mM sodium molybdate, no significant difference in k+1 and k-1 values could be found between cytosolic receptor preparations from normal and malignant specimens. The values obtained for k+1 (mean +/- SD) were 5 +/- 2 X 10(6)M-1 min-1 (N = 3) and 5 +/- 2 X 10(6)M-1 (N = 5); k-1 values of 23 +/- 4 X 10(-4) min-1 (N = 4) and 25 +/- 3 X 10(-4) min-1 (N = 5) were obtained for normal and malignant tissues respectively. Similar Nmax values were also obtained for normal [(mean +/- SD) 26 +/- 10 fmol/mg cytosolic protein (N = 5)] and malignant [20 +/- 9 fmol/mg protein (N = 7)] tissues. A statistically significant difference was found however, between k-1 values measured on [3H]androgen receptor complexes of nuclear extracts; values of 15 +/- 3 X 10(-4) min-1 (N = 4) and 9 +/- 1 X 10(-4) min-1 (N = 6) were found for normal and malignant tissue preparations respectively. This was also accompanied by a higher level of androgen receptors in nuclear extracts of malignant [Nmax, 308 +/- 171 fmol/g of tissue (N = 8)] compared to normal [Nmax, 68 +/- 11 fmol/g of tissue (N = 5)] tissues. The cytosolic [3H]androgen receptor complexes prepared from normal tissues sedimented mainly in the 8-9S area on sucrose density gradient whereas those from malignant tissues sedimented 50% in the 8-9S area and 50% in the 4S area. In conclusion, in this study, we found a different sedimentation profile of androgen-receptor complexes from the cytosol of prostatic cancers compared to normal as well as a diminution of their dissociation rate constant in nuclei.

Induction of Androgen Receptor by 1α,25-Dihydroxyvitamin D3and 9-cis Retinoic Acid in LNCaP Human Prostate Cancer Cells1

“…The expression of the AR gene has been found to be induced by a number of agents in several systems, such as the rat ventral prostate (31), and in LNCaP human prostate cancer cells (32,33). Growth factors such as FSH, EGF, and TGF-␤ regulate AR gene expression (34,35).…”