PPAR[alpha]/[gamma] Expression and Activity in Mouse and Human Melanocytes and Melanoma Cells

• Published in: Pharmaceutical research 2008-06, Vol.25 (6), p.1327
• Main Authors: Eastham, Linda L, Mills, Caroline N, Niles, Richard M
• Format: Article
• Language: English
• Subjects: Cellular biology; Gene expression; Human body; Pharmacology; Rodents; Skin cancer
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-007-9524-9

We examined the expression of PPARs and the effects of PPAR[alpha] and PPAR[gamma] agonists on growth of mouse and human melanocytes and melanoma cells. PPAR[alpha],[beta], and PPAR[gamma] mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPAR[alpha] mRNA levels were determined by QuantiGene assay. PPAR[alpha] and PPAR[gamma] protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter gene assay, while knockdown of PPAR[alpha] expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPAR[alpha] and PPAR[gamma] protein compared to melanocytes. PPAR[alpha] mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPAR[alpha] in human melanoma cells did not alter cell proliferation or morphology. PPAR[gamma]-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPAR[alpha]-selective agonists had limited effects. Increased expression of PPAR[alpha] in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPAR[gamma] agonists may be useful for arresting the growth of some melanomas. [PUBLICATION ABSTRACT]