CCAAT/enhancer-binding protein δ:: A molecular target of 1,25-dihydroxyvitamin D3 in androgen-responsive prostate cancer LNCaP cells

1,25-Dihydroxyvitamin D-3 [1,25(OH)(2)D-3], the active metabolite of vitamin D-3, inhibits the proliferation of prostate cancer cells. However, the molecular mechanisms by which 1,25(OH)(2)D-3 inhibits the proliferation of these cells remain to be fully elucidated. In this study, we used microarray technology to identify target genes of 1,25(OH)2D3 in androgen-responsive prostate cancer LNCaP cells. 1,25(OH)(2)D-3 up-regulated CCAAT/enhancer-binding protein delta (C/EBP delta) by similar to 5-fold in these cells. Knockdown of C/EBP delta expression by RNA interference showed that C/EBP delta is essential for the significant growth inhibition of LNCaP cells in response to 1,25(OH)(2)D-3 treatment. Moreover, we found that 1,25(OH)(2)D-3 induced C/EBP delta in other cancer cells, including the estrogen receptor (ER)-expressing MCF-7 and T47D breast cancer cells that are sensitive to the growth inhibitory effects of 1,25(OH)(2)D-3. On the other hand, 1,25(OH)(2)D-3 was not able to induce C/EBP delta in either androgen receptor-negative PC-3 and DU145 or ER-negative breast cancer MDA-MB-231 cells that were relatively resistant to growth inhibition by 1,25(OH)(2)D-3. Furthermore, forced expression of C/EBP delta in prostate cancer LNCaP as well as breast cancer MCF-7 and T47D cells dramatically reduced their clonal growth. Taken together, forced expression of C/EBP delta in cancer cells may be a promising therapeutic strategy.