Role of Melanin in Oncogenesis
Abstract
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 moles and infrequently, malignant moles that progress to melanoma. My hypothesis in the current research project is that excess melanin production in melanocytes may cause physico-chemical constraints on the metabolic activities of DNA and RNA, which, in rare instances, may induce pro-survival responses, including mutations, in cellular DNA. This may lead to selective transcription and/or translation that support oncogenic transformation of these cells. To test this hypothesis, I induced long-term production of excess melanin in normal melanocytes using chronic tyrosine exposure and chronic UV radiation treatment. I then examined the cell biological changes induced by excess melanin production in these cells and found that excess melanin production caused a small increase in their proliferation. More interestingly, chronic melanin induction in melanocytes derived from fair-skinned individuals, but not dark-skinned individuals increased the migration and soft-agar colony formation ability of the melanocytes, suggesting that melanin or melanin biosynthetic machinery may play a role in oncogenic transformation. Gene expression profiling of low melanin and high melanin containing normal melanocytes revealed distinct expression patterns associated with different signaling networks. Functional studies are currently underway to determine if knock-down of tyrosinase activity, which decreases melanin content in cells, abrogates the transformative potential of chronic melanin induction.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 28, 2011
- Accession Number
- ADA546078
Entities
People
- Vashisht G. Yennu-nanda
Organizations
- University of Texas at Austin