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Journal of Skin Cancer
Volume 2014, Article ID 439205, 10 pages
http://dx.doi.org/10.1155/2014/439205
Research Article

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

1Laboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA
2Department of Dermatology, School of Medicine, Wayne State University, Detroit, MI 48201, USA
3Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA
4Pinkus Dermatopathology Laboratory, Monroe, MI 48162, USA
5Biostatistics, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA
6Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA
7Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA
8Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA

Received 24 January 2014; Revised 2 April 2014; Accepted 15 April 2014; Published 6 May 2014

Academic Editor: Selma Ugurel

Copyright © 2014 Karli Rosner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We have previously demonstrated that Rad6 and β-catenin enhance each other's expression through a positive feedback loop to promote breast cancer development/progression. While β-catenin has been implicated in melanoma pathogenesis, Rad6 function has not been investigated. Here, we examined the relationship between Rad6 and β-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 nuclear β-catenin. β-Catenin was exclusively localized on the cell membrane of 55% of primary, 62% of metastatic melanomas, and only 10% of nevi. Cytoplasmic β-catenin was detected in 90% of nevi, 17% of primary, and 8% of metastatic melanoma, whereas 28% of primary and 30% of metastatic melanomas exhibited β-catenin at both locations. These data suggest that melanoma development and progression are associated with Rad6 upregulation and membranous redistribution of β-catenin and that β-catenin and Rad6 play independent roles in melanoma development.