Vitamin D and prostate cancer: The role of membrane initiated signaling pathways in prostate cancer progression

1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) has been demonstrated to mediate both genomic and non-genomic responses in prostate cancer (CaP) cells. Here, we give an overview of membrane initiated 1,25(OH)(2)D-3 signaling in prostate cancer cell progression. The presence of PDIA3 was investigated and homologous modeling of the putative PDIA3 receptor complex was conducted. Furthermore, the cellular distribution of nVDR was analyzed. We could show that both nVDR and PDIA3 are expressed in the prostate cancer cell lines investigated. The homologous modeling of PDIA3 showed that the receptor complex exists in a trimer formation, which suggests for allosteric activity. Our findings support previous reports and suggest that 1,25(OH)(2)D-3 is an important therapeutic agent in inhibiting prostate cancer progression. Furthermore, our data show that 1,25(OH)(2)D-3 regulate prostate cell biology via multiple pathways and targeting specific pathways for 1,25(OH)(2)D-3 might provide more effective therapies compared to the vitamin D therapies currently clinically tested. (C) 2010 Elsevier Ltd. All rights reserved.