Androgen modulation of prostate cancer cell androgen receptor content is cell line specific.
Using methods for cell lysis and fractionation which yield essentially quantitative recovery of rat prostate cancer cell cytosolic and nuclear androgen receptors, we examined androgen modulation of androgen receptor content of clonally derived prostate cancer cell lines. We showed that testosterone elicited a concentration-dependent 2.3-fold increase in T5 cell androgen receptor content which was maximum after 48 h and was maintained through at least 72 h of culture. Testosterone caused only a 1.4-fold elevation in D2 cell androgen receptor content which was maximum between 6 and 12 h of culture and was maintained through at least 72 h culture. In contrast, testosterone did not cause a change in C3 cell androgen receptor content. Cycloheximide inhibition showed that both the testosterone-mediated increase in and maintenance of basal prostate cancer cell androgen receptor content required protein synthesis. Because testosterone and the nonmetabolizable androgen R1881 were essentially equipotent as effectors of the increase in T5 cell androgen receptor content, findings using testosterone appear to represent maximum effects. RU 23908 antagonized both R1881 and testosterone promoted elevations of prostate cancer cell androgen receptor content. Effectiveness of RU 23908 was comparable to the relative binding affinity of R1881, testosterone and RU 23908 for androgen receptors. This implies that at least part of the androgen-promoted increase in prostate cancer cell androgen receptor content is mediated through the action of androgen receptors and suggests that androgen receptors may act as both cis and trans regulatory elements. The mechanisms which determine basal or androgen-modulated prostate cancer cell androgen receptor content remain to be elucidated.
Lin
A L
AL
Department of Cellular and Molecular Biology, Southwest Foundation for Biomedical Research, San Antonio, TX 78284.
Shain
S A
SA
D000728:Androgens / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000032:analysis / Q000378:metabolism / Q000648:ultrastructure; D004963:Estrenes / Q000378:metabolism; D008297:Male; D015741:Metribolone; D011471:Prostatic Neoplasms / Q000032:analysis / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D011944:Receptors, Androgen / Q000032:analysis / Q000378:metabolism / Q000648:ultrastructure*; D045165:Testosterone Congeners / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D000906:Antibodies; D004963:Estrenes; D011944:Receptors, Androgen; D045165:Testosterone Congeners; D015741:Metribolone