Melanoma Development and Progression Are Associated with Rad6 Upregulation andβ-Catenin Relocation to the Cell Membrane

Abstract

We have previously demonstrated that Rad6 andβ-catenin enhance each other's expression through a positive feedback loop to promote breast cancer development/progression. Whileβ-catenin has been implicated in melanoma pathogenesis, Rad6 function has not been investigated. Here, we examined the relationship between Rad6 andβ-catenin in melanoma development and progression. Eighty-eight cutaneous tumors, 30 nevi, 29 primary melanoma, and 29 metastatic melanomas, were immunostained with anti-β-catenin and anti-Rad6 antibodies. Strong expression of Rad6 was observed in only 27% of nevi as compared to 100% of primary and 96% of metastatic melanomas.β-Catenin was strongly expressed in 97% of primary and 93% of metastatic melanomas, and unlike Rad6, in 93% of nevi. None of the tumors expressed nuclearβ-catenin.β-Catenin was exclusively localized on the cell membrane of 55% of primary, 62% of metastatic melanomas, and only 10% of nevi. Cytoplasmicβ-catenin was detected in 90% of nevi, 17% of primary, and 8% of metastatic melanoma, whereas 28% of primary and 30% of metastatic melanomas exhibitedβ-catenin at both locations. These data suggest that melanoma development and progression are associated with Rad6 upregulation and membranous redistribution ofβ-catenin and thatβ-catenin and Rad6 play independent roles in melanoma development.