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Skin Hypoxia: A Promoting Environmental Factor in Melanomagenesis

Barbara Bedogni and Marianne Broome Powell

volume 5 | issue 12

15 june 2006
Pages: 1258 - 1261

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Melanomagenesis is a complex phenomenon in which environmental, genetic and host factors play a role. Sun burns in early childhood are a known risk factor in melanoma development. Alteration of prosurvival genes such as Ras and Akt and loss of function of the p16INK4a-CDK4/6-pRb and p14ARF-HDM2-p53 pathways are strongly associated with human melanoma. We have demonstrated that normally occurring skin hypoxia represents a previously unappreciated host promoting factor in melanomagenesis. Melanocytes that express oncogenes such as Akt, and are therefore genetically unstable, show a transform phenotype only in a mild hypoxic environment that resembles the hypoxic status of the skin. Hypoxia, therefore, is not just a prerogative of advanced neoplasia; physiologic tissue hypoxia, through the activity of HIF1α, can function as a promoting factor in tumorigenesis.



We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.