We have investigated expression of
vitamin D receptor (VDR) and
peroxisome proliferator-activated receptors (
PPAR)alpha, delta, gamma in primary cultured normal melanocytes (NHM),
melanoma cell lines (MeWo, SK-Mel-5, SK-Mel-25, SK-Mel-28), a cutaneous
squamous cell carcinoma cell line (SCL-1) and an immortalized sebocyte cell line (SZ95). LNCaP
prostate cancer cells, MCF-7
breast cancer cells and embryonic kidney cells (HEK-293) were used as controls. VDR and
PPAR mRNA were detected, quantitated and compared in these cell lines using real-time quantitative polymerase chain reaction (RTqPCR). The expression patterns of these
nuclear receptors (NRs) varied strongly between the different cell lines according to their origin.
PPARdelta and
PPARgamma were less strongly expressed in the
melanoma cell lines and in the other skin-derived cell lines as compared to the control cell lines.
PPARalpha and VDR were stronger expressed in the 1,25(OH)(2)D(3)-sensitive
melanoma cells (MeWo and in SK-Mel-28) than in the 1,25(OH)(2)D(3)-resistent
melanoma cell lines (SK-Mel-5 and SK-Mel-25) or in NHM. Interestingly, VDR expression was increased by the treatment with
1,25(OH)(2)D(3) in 1,25(OH)(2)D(3)-sensitive
melanoma cells but not in 1,25(OH)(2)D(3)-resistent
melanoma cell lines.
1,25(OH)(2)D(3) increased the expression of
PPARalpha in almost all cell lines analyzed. Our results indicate a cross-talk between VDR- and
PPAR-signaling pathways in various cell types including
melanoma cells. Further investigations are required to investigate the physiological and pathophysiological relevance of this cross-talk. Because VDRand
PPAR-signaling pathways regulate a multitude of genes that are of importance for a multitude of cellular functions including cell proliferation, cell differentiation, immune responses and apoptosis, the provided link between VDR and
PPAR may open important new perspectives for treatment and prevention of
melanoma and other diseases.