PPARalpha/gamma expression and activity in mouse and human melanocytes and melanoma cells

We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 hu...

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Bibliographic Details
Published in:Pharmaceutical research 2008-06, Vol.25 (6), p.1327-1333
Main Authors: Eastham, Linda L, Mills, Caroline N, Niles, Richard M
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cell Proliferation
Humans
Melanocytes - metabolism
Melanoma - metabolism
Mice
PPAR alpha - agonists
PPAR alpha - analysis
PPAR alpha - genetics
PPAR alpha - physiology
PPAR gamma - agonists
PPAR gamma - analysis
PPAR gamma - genetics
PPAR gamma - physiology
RNA, Messenger - analysis
Transcriptional Activation
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Summary:We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma 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 PPARalpha mRNA levels were determined by QuantiGene assay. PPARalpha and PPARgamma 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 PPARalpha expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPARalpha and PPARgamma protein compared to melanocytes. PPARalpha mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARalpha in human melanoma cells did not alter cell proliferation or morphology. PPARgamma-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARalpha-selective agonists had limited effects. Increased expression of PPARalpha in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARgamma agonists may be useful for arresting the growth of some melanomas.
ISSN:0724-8741
DOI:10.1007/s11095-007-9524-9