TNF-alpha-related apoptosis-inducing ligand decoy receptor DcR2 is targeted by androgen action in the rat ventral prostate.
The apoptotic cell death process in the prostate is known to be under the control of androgens. Tumor necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF-alpha family of cytokines, known to induce apoptosis upon binding to its death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2. Two additional TRAIL receptors, DcR1/TRAIL-R3 and DcR2/TRAIL-R4, lack functional death domains and act as decoy receptors for TRAIL. In this study, we examined whether TRAIL and cellular receptors expression was targeted by androgens during the apoptotic cell death process in the hormone sensitive ventral prostate. The role of androgens was investigated using two sets of experiment. (1) Androgen deprivation associated with an apoptotic process resulted in a decrease in DcR2 mRNA and protein expression in the ventral prostate 3 days after castration. Testosterone administration to castrated adult rats prevented the decrease in DcR2 mRNA and protein levels in the ventral prostate. In contrast, DcR2 expression was modified, neither in the dorsolateral nor in the anterior prostate following castration. No changes were observed in DR4, DR5, DcR1, and TRAIL mRNA and protein levels in prostate after castration. (2) A specific decrease in DcR2 expression was observed in the ventral prostate after treatment of rats with the anti-androgen flutamide. Together, the present results suggest that testosterone specifically controls DcR2 expression in the adult rat ventral prostate. Androgen withdrawal, by reducing DcR2 expression, might leave the cells vulnerable to cell death signals generated by TRAIL via its functional receptors.
Vindrieux
David
D
Institut National de la Santé et de la Recherche Médicale, Communications Cellulaires en Biologie de la Reproduction, Faculté de Médecine Lyon-Sud, Oullins Cedex, France.
Réveiller
Marie
M
Florin
Anne
A
Blanchard
Cécile
C
Ruffion
Alain
A
Devonec
Marian
M
Benahmed
Mohamed
M
Grataroli
Renée
R
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000502:physiology; D002369:Castration; D005485:Flutamide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D053221:TNF-Related Apoptosis-Inducing Ligand; D013739:Testosterone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology
D000726:Androgen Antagonists; D000728:Androgens; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505655:Tnfsf10 protein, rat; D014409:Tumor Necrosis Factor-alpha; C509611:decoy receptor 2, rat; D013739:Testosterone; D005485:Flutamide