Loss of keratinocytic RXRα combined with activated CDK4 or oncogenic NRAS generates UVB-induced melanomas via loss of p53 and PTEN in the tumor microenvironment.

ABSTRACT:

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Understanding the molecular mechanisms behind formation of melanoma, the deadliest form of skin cancer, is crucial for improved diagnosis and treatment. One key is to better understand the cross-talk between epidermal keratinocytes and pigment-producing melanocytes. Here, using a bigenic mouse model system combining mutant oncogenic NRAS(Q61K) (constitutively active RAS) or mutant activated CDK4(R24C/R24C) (prevents binding of CDK4 by kinase inhibitor p16(INK4A)) with an epidermis-specific knockout of the nuclear retinoid X receptor alpha (RXRα(ep-/-)) results in increased melanoma formation after chronic ultraviolet-B (UVB) irradiation compared with control mice with functional RXRα. Melanomas from both groups of bigenic RXRα(ep-/-) mice are larger in size with higher p

SUBMITTER: Coleman DJ 

PROVIDER: S-EPMC4297739 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature