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PPARα/γ Expression and Activity in Mouse and Human Melanocytes and Melanoma Cells

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Abstract

Purpose

We examined the expression of PPARs and the effects of PPARα and PPARγ agonists on growth of mouse and human melanocytes and melanoma cells.

Methods

PPARα,β, and PPARγ 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 PPARα mRNA levels were determined by QuantiGene assay. PPARα and PPARγ 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 PPARα expression was achieved by transient transfection of siRNA.

Results

Both mouse and human melanoma cells produced more PPARα and PPARγ protein compared to melanocytes. PPARα mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARα in human melanoma cells did not alter cell proliferation or morphology. PPARγ-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARα-selective agonists had limited effects.

Conclusion

Increased expression of PPARα in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARγ agonists may be useful for arresting the growth of some melanomas.

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Abbreviations

CDK:

cyclin depdendent protein kinase

GAPDH:

glyceraldehyde phosphate dehydrogenase

MCAD:

medium chain acyl CoA dehydrogenase

PPAR:

peroxisome proliferator activated receptor

PPRE:

peroxisome proliferator response element

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Acknowledgement

The authors would like to thank Dr. Zalfa Abdel-Malik, University of Cincinnati, for supplying human melanocyte cultures for some of our initial studies. We also thank Margaret McFarland for preparing the figures. This study was supported in part by grants CA59530 from the NCI, NIH, CA59539/S from the MARC program NIH, and P20 RR20180 from the Division of Research Resources, NIH.

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Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, One John Marshall Drive, Huntington, West Virginia, 25755, USA

    Linda L. Eastham, Caroline N. Mills & Richard M. Niles

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  1. Linda L. Eastham
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  2. Caroline N. Mills
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  3. Richard M. Niles
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Correspondence to Richard M. Niles.

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Eastham, L.L., Mills, C.N. & Niles, R.M. PPARα/γ Expression and Activity in Mouse and Human Melanocytes and Melanoma Cells. Pharm Res 25, 1327–1333 (2008). https://doi.org/10.1007/s11095-007-9524-9

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  • DOI: https://doi.org/10.1007/s11095-007-9524-9

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