Jun 4, 2010

Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Ana L KadekaroZalfa A Abdel-Malek

Abstract

The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls ge...Continue Reading

Mentioned in this Paper

Melanocyte
Cancer-Predisposing Gene
MC1R Protein
DNA Repair
Genomic Stability
Antioxidants
Melanoma vaccine
Hydrogen Peroxide Biosynthetic Process
Skin/Hair/Eye Pigmentation, Variation In,2 (Disorder)
MC1R gene

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