Activation of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)(2)D(3) in melanoma cell lines and other skin-derived cell lines.
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.
Sertznig
Pit
P
Seifert
Markus
M
Tilgen
Wolfgang
W
Reichrath
Jörg
J