Calcitriol inhibits growth response to Platelet-Derived Growth Factor-BB in human prostate cells

Calcitriol, a hormonal form of Vitamin D, regulates growth of normal and cancer cells of various origins by modulation of peptide growth factors signaling. Platelet-Derived Growth Factor (PDGF) signaling pathway is involved in prostate cancer progression. We studied the expression of PDGF receptors in human prostate primary stromal cells and cancer epithelial cell lines and growth response to PDGF-BB isoform. We found that the expression of PDGF receptors and PDGF-BB-mediated cell growth are regulated by calcitriol in prostate cells. Quantitative RT-PCR analysis revealed a lower level of mRNA for PDGF receptors in LNCaP and PC-3 cells than in primary stromal cells. Western blotting showed a high amount of PDGFR alpha and beta proteins in primary stromal cells that could not be detected in LNCaP, which may explain the resistance of LNCaP cells to growth-promoting effect of PDGF-BB. Addition of Epidermal Growth Factor (EGF) to the culture medium induces the expression of PDGFR beta and restores responsiveness of LNCaP to PDGF-BB to some extent. Calcitriol down-regulates PDGFR beta expression and negatively regulates PDGF-mediated cell growth. Calcitriol does not affect PDGFR alpha and PDGF-B mRNA expression. We suggest that inhibition of PDGFR beta expression by calcitriol might reduce responsiveness of prostate cells to mitogenic action of PDGF-BB. (c) 2005 Elsevier Ltd. All rights reserved.