Fig. 2
Melanomas from RXRα ep−/−|TyrNRAS Q61K|Cdk4 R24C/R24C mice display enhanced proliferation, malignant conversion and angiogenesis relative to their controls. a, b Fluorescent IHC for proliferation marker PCNA (red) and melanocyte marker TYRP1 (green). A trend in overall increase of PCNA+/TYRP1+ cells was observed in lesions from Rxrαep−/− mice compared to RxrαL2/L2 controls in combination with Tyr-NRASQ61K and Cdk4R24C mutations in no UVB treated mice (a) and single neonatal UVB treated mice (b). c, d Bar-graph represents PCNA + |TYRP2+ melanocytes/ field in no UVB and acute UVB treatment respectively. e, f IHC using antibody cocktail of antibodies directed against malignant melanoma antigens HMB45 and MART-1 (red). Overall, more positive staining was observed in lesions from the triple knockout mice with RXRα ep−/− ablation compared to bigenic mice with their respective RxrαL2/L2 controls mutations in no UVB treated mice (e) and single neonatal UVB treated mice (f). g, h IHC for tumor angiogenesis marker CD31 (red). Overall, more prominent staining was observed in lesions from trigenic RXRα ep−/− mice compared to controls. Loss of epidermal Rxrα results in lesions with multicellular CD31+ blood vessels (g, right panel) in mice with no UVB treatment while acute UVB treated mice resulted in larger multicellular CD31+ blood vessels (h, right panel). a, b, c, d, e, f, g, h White dashed lines, artificially added, indicate epidermal-dermal junction. Blue color corresponds to DAPI staining of the nuclei. E = Epidermis, D = Dermis. Scale bars = 50 μm. Statistical relevance indicated as follows; * = p < 0.05