Combinational Effects of Retinoid-X-Receptor α (RXRα) Ablation with Oncogenic Mutations Cdk4[Superscript R24C/R24C] or N-Ras[Superscript Q61K/Q61K] after Ultraviolet Radiation Induced Melanoma Development
Recent research has identified Retinoid-X-Receptorα (RXRα), a nuclear receptor involved in ligand mediated transcription, as having a protective function against the malignant transformation of melanocytes after treatment with chemical carcinogens. This study used mice selectively lacking keratinocytic RXRα in combination with an oncogenic mutation, either Cdk4[Superscript R24C/R24C] or N-Ras[Superscript Q61K/Q61K], to investigate how two different cellular proliferation mechanisms react to chronic UV exposure. RXRα[Superscript ep-/-]/ Cdk4[Superscript R24C/R24C] bigenic mice showed increased melanoma development, amplified compaction and penetration of melanin in the dermal and epidermal layers, a greater number of tumors, and a larger population of proliferating melanocytes in the epidermis compared to control mice. Similarly, RXRα[Superscript ep-/-]/N-Ras[Superscript Q61K/Q61K] bigenic mice also showed a greater susceptibility to UV induced melanoma formation, although the concentrated pigmentation of the skin made quantitative analysis difficult. Overall, the degree of melanocytic compaction and infiltration in mice lacking RXRα was much greater than those wild-type for RXRα.