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Cross‐regulation of peroxisome proliferator‐activated receptor‐ (PPAR) and vitamin D receptor‐signaling pathways in melanoma cells
Author(s) -
Sertznig P.,
Seifert M.,
Tilgen W.,
Reichrath J.
Publication year - 2008
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2008.00742_5.x
Subject(s) - nuclear receptor , calcitriol receptor , peroxisome proliferator activated receptor , signal transduction , receptor , cancer research , biology , transcription factor , microbiology and biotechnology , endocrinology , medicine , biochemistry , gene
Peroxisome proliferator‐activated receptors (PPARs) are adopted orphan nuclear hormone receptors, that regulate lipid, glucose, and amino acid metabolism. In recent studies PPAR‐ligands and other agents influencing PPAR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in a variety of human cancers. Thus modulating PPAR signaling pathways represent a potential novel strategy for cancer prevention and treatment. In addition, transcription of PPARs has been shown to be directly regulated by 1,25(OH)2D3. To further evaluate the potential role of PPAR‐ligands and 1,25(OH)2D3 in melanoma therapy, we have asked the following questions: (I) Do PPAR‐ligands and/or 1,25(OH)2D3 regulate cell proliferation in MeWo cells (II) Do PPAR‐ligands and/or 1,25(OH)2D3 modulate expression of corresponding nuclear receptors in MeWo cells? (III) Can we find hinds for a cross‐regulation of PPAR‐ and VDR‐signaling pathways in MeWo cells? Using real time PCR, we have characterized expression of PPARα, ‐δ ,‐γ and VDR in the melanoma cell line MeWo. We show that PPARα and ‐δ are much stronger expressed in melanoma cell lines than PPARγ. We demonstrate antiproliferative effects of various PPAR‐ligands and/or 1,25(OH)2D3 on melanoma cell lines. PPAR‐ligands and/or 1,25(OH)2D3 significantly modulate PPAR‐ and VDR‐Expression. This suggests that PPAR‐ and VDR‐signaling pathways are interconnected by reciprocal effects of the activated receptors. In conclusion, our data support the concept that PPARs may be of importance for pathogenesis, progression, and therapy of malignant melanoma.