Skin hypoxia: a promoting environmental factor in melanomagenesis.
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 p16(INK4a)-CDK4/6-pRb and p14(ARF)-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 HIF1alpha, can function as a promoting factor in tumorigenesis.
Bedogni
Barbara
B
Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California, USA.
Powell
Marianne Broome
MB
D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D051057:Proto-Oncogene Proteins c-akt