Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

✍ Scribed by Culig, Zoran; Hobisch, Alfred; Hittmair, Anton; Cronauer, Marcus V.; Radmayr, Christian; Zhang, Ju; Bartsch, Georg; Klocker, Helmut

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 297 KB
• Volume: 32
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19970701)32:2<106::aid-pros5>3.0.co;2-k

✦ Synopsis

Background:

We investigated modulation of androgen receptor (ar) activity in prostatic tumor cells by luteinizing hormone-releasing hormone (lhrh)-induced increase of the intracellular cyclic adenosine monophosphate (camp) level.

Methods:

Ar transactivation activity was assessed in transiently transfected du-145 and in lncap cells.

Results:

Lhrh and camp derivative, respectively, induced reporter gene activity to about 15% of the maximal level in du-145 cells transfected with an ar expression vector and an androgen-inducible reporter gene. lhrh or the camp analogue acted synergistically in combination with low concentrations of androgen thus lowering the androgen concentration required for maximal ar activation by a factor of 100. a similar activation of the ar by camp analogue was observed in lncap cells when enhancement of androgen-induced secretion of prostate-specific antigen was determined. the two nonsteroidal antiandrogens hydroxyflutamide and casodex(r) inhibited reporter gene activity.

Conclusions:

The ar is synergistically activated by low doses of androgen and lhrh or the second messenger camp. this may have implications for the treatment of advanced prostate cancer.