[Androgens stimulate the expression of SOCS-3 and inhibits their effect on proliferation and secretion].
OBJECTIVE
Suppressors of cytokine signalling (SOCS) are induced by interleukins and peptide hormones. These molecules prevent the activation of diverse signalling pathways in benign and malignant cells. In previous studies, we showed that SOCS-3 is expressed in most prostate cancer cell lines and tissue specimens. In the present study we investigated the effects of androgen on the regulation of SOCS-3 in prostate cancer cell lines.


METHODS
SOCS-3 expression was determined with PCR and Western blot techniques. The activity of the SOCS-3 promoter was measured with the luciferase test. We measured proliferation with (3)H-thymidine assay.


RESULTS
We show that androgen induces the expression of SOCS-3 in two prostate cancer cell lines. The non-steroidal anti-androgen bicalutamide is able to block the induction of SOCS-3 -expression. Androgenic hormones did not induce the expression of SOCS-3 mRNA or its promoter activity. In LNCaP-IL-6- cells transfected with the inducible Tet-On construct SOCS-3 expression was induced. The effects of androgenic hormones on the proliferation and induction of PSA were -diminished in the presence of SOCS-3.


CONCLUSIONS
Our results show that androgenic -regulation of SOCS-3 leads to inhibition of prolif-eration and secretion in human prostate cancer.
Neuwirt
H
H
Univ.-Klinik für Urologie, Medizinische Universität Innsbruck, Innsbruck, Osterreich.
Puhr
M
M
Cavarretta
I T
IT
Mitterberger
M
M
Hobisch
A
A
Culig
Z
Z
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000502:physiology*; D000813:Anilides / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D045165:Testosterone Congeners / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D009570:Nitriles; D012333:RNA, Messenger; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D045165:Testosterone Congeners; D014105:Tosyl Compounds; D015741:Metribolone; C053541:bicalutamide; D018844:Cyclin-Dependent Kinases; D017430:Prostate-Specific Antigen; D004318:Doxycycline