Interleukin-6 is a potent inducer of S100P, which is up-regulated in androgen-refractory and metastatic prostate cancer.
Elevated circulating interleukin-6 (IL6) and up-regulated S100P in prostate cancer (PCa) specimens correlate independently with progression to androgen-independent and metastatic PCa. The cause of up-regulated S100P levels in advanced PCa remains to be determined. We investigated the possibility that IL6 is an inducer of S100P. Determination of mRNA and protein levels by real-time PCR and Western blotting revealed that IL6 is a more potent inducer of S100P than the synthetic androgen, R1881, in the LNCaP/C4-2B model of PCa progression. IL6 did not require androgen to induce S100P in these cells, which express a functional androgen receptor (AR). Like R1881, IL6 was unable to induce S100P in PC3 cells that lack a functional AR. IL6 did not strongly induce the AR-dependent genes PSA and KLK2 and, contrary to R1881, down-regulated Cyr61/CCN1, a potential marker that is down-regulated in PCa. Epidermal growth factor (EGF), which like IL6 is a non-androgen activator of the AR, did not induce S100P. The data identifies a unique gene-induction profile for IL6 and suggests that IL6 may require a functional AR for S100P induction. A link between elevated IL6 and up-regulated S100P in androgen-refractory and metastatic PCa is postulated.
Bernard O'Brien Institute of Microsurgery, University of Melbourne, 42 Fitzroy Street, Fitzroy, Vic. 3065, Australia. a.hammacher@pgrad.unimelb.edu.au
Annet
A
Hammacher
Erik W
EW
Thompson
Elizabeth D
ED
Williams
D000728:Androgens / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects*
D000728:Androgens; D002135:Calcium-Binding Proteins; D015850:Interleukin-6; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; C103003:S100P protein, human; D015741:Metribolone