Role of Melanin in Oncogenesis
Final rept. 1 Feb-31 Jul 2011
M D ANDERSON CANCER CENTER HOUSTON TX
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Increased solar radiation and other unknown factors induce excess melanin production in melanocytes accumulated in localized areas of the skin, leading to formation of benign nevi and infrequently, dysplastic nevi that may progress to melanoma. I hypothesized that excess melanin production in melanocytes of such nevi may cause physico-chemical constraints on the metabolic activities of DNA and RNA, which, in rare instances, may induce pro-survival responses, including oncogenic mutations, in cellular DNA. This may lead to selective transcription andor translation that support oncogenic transformation of one or more of these cells. To test this hypothesis, long-term production of excess melanin in melanocytes derived from fair-skinned and dark-skinned individuals was induced with chronic tyrosine exposure or chronic UV-radiation treatment. Long-term melanin production in cells from fair-skinned individuals caused a small increase in their proliferation. Chronic melanin production over a period of six months revealed unique gene expression patterns associated with growth promoting signaling networks in melanocytes from fair-skinned individuals. Functional cell biological analyses revealed that these effects resulted in increased proliferation and transformative potential of the melanocytes derived from fair-skinned, but not dark-skinned individuals. This study suggests that melanin pigment may play an important role in the oncogenic transformation of melanocytes from fair-skinned individuals.
- Anatomy and Physiology