Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaPhuman prostate cancer cells

Genes that are regulated by androgens in the human prostate are believed to play an essential role in prostate physiology and they may also be involve d in the proliferative response of prostate cancer cells to androgens. We u sed a cDNA subtraction approach to identify novel androgen-regulated transc ripts in LNCaP cells that were exposed to 0.1 nM R1881 for 24 h We report h ere that SPAK, a recently identified STE20/SPS1-related kinase that modulat es p38 MAP kinase activity, exhibited increased expression in androgen-trea ted LNCaP cells. Androgen regulation of SPAK was both dose- and time-depend ent. R1881-induced SPAK expression was completely abrogated by the antiandr ogen casodex and by actinomycin D indicating that androgen induction of SPA K requires the androgen receptor and transcription. Cycloheximide caused a partial inhibition of R1881-induced SPAK expression which suggests that and rogen induction of SPAK expression may require synthesis of additional prot eins. Northern blot and ribonuclease protection assays demonstrated that SP AK is expressed at high levels in normal human testes and prostate, as well as in a number of breast and prostate cancer cell lines. These results ide ntify SPAK, a member of a key cell signalling pathway, as an androgen-respo nsive gene in LNCaP cells. We hypothesize that SPAK may mediate androgen ac tion in the normal and cancerous prostate gland. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.