Pim1 regulates androgen-dependent survival signaling in prostate cancer cells.
BACKGROUND
Pim1 overexpression was found to be associated with more advanced prostate cancer. Interleukin-6 (IL-6) induces Pim1 expression and is often found elevated after androgen-ablative therapy.


METHODS
Tumor tissue from 31 selected prostate cancer patients and cell lines were studied immunohistochemically for c-myc, Pim1, STAT3, pSTAT3-Tyr705, and androgen receptor (AR) expression. The effect of Pim1 on androgen dependence in prostate cancer was studied in transgene cell lines.


RESULTS
Pim1 expression was increased in high-grade prostate tumors (Gleason >7), irrespective of androgen status, was highest in hormone refractory prostate cancer and correlated to pSTAT3-Tyr705 expression levels. Co-expression of Pim1 and MYC was observed specifically after androgen ablation. Pim1 expression could be induced in LNCaP and PC3 cells by IL-6. Pim1 overexpression in PC3 and PNCaP increased the transcriptional activity of the AR at low levels of dihydrotestosterone. Consequently, Pim1 expression increased LNCaP cell survival specifically at castrate levels of androgen.


CONCLUSIONS
Pim1 expression was increased in primary tumor samples after androgen ablation. Pim1 overexpression increased AR transcriptional activity in a ligand-dependent manner in prostate cancer cell lines, resulting in enhanced cell survival at castrate levels of androgen.
van der Poel
H G
HG
Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands. h_vanderpoel @ hotmail.com
Zevenhoven
J
J
Bergman
A M
AM
D000728:Androgens / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009369:Neoplasms / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D019076:Transgenes
D000728:Androgens; D015850:Interleukin-6; D008024:Ligands; D016271:Proto-Oncogene Proteins c-myc; D011944:Receptors, Androgen; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1