title: Melanoma Development and Progression Are Associated with Rad6 Upregulation and β -Catenin Relocation to the Cell Membrane.
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.
authors.affiliation: Laboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA ; Department of Dermatology, School of Medicine, Wayne State University, Detroit, MI 48201, USA ; Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Karli
authors.identifier: 0000-0002-5033-7432
authors.initials: K
authors.lastname: Rosner
authors.affiliation: Department of Dermatology, School of Medicine, Wayne State University, Detroit, MI 48201, USA ; Pinkus Dermatopathology Laboratory, Monroe, MI 48162, USA.
authors.forename: Darius R
authors.initials: DR
authors.lastname: Mehregan
authors.affiliation: Laboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA ; Department of Dermatology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Evangelia
authors.identifier: 0000-0001-7511-4457
authors.initials: E
authors.lastname: Kirou
authors.affiliation: Biostatistics, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA ; Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Abrams
authors.affiliation: Biostatistics, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA ; Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Seongho
authors.identifier: 0000-0002-9575-8847
authors.initials: S
authors.lastname: Kim
authors.affiliation: Pinkus Dermatopathology Laboratory, Monroe, MI 48162, USA.
authors.forename: Michelle
authors.identifier: 0000-0002-1472-0194
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Laboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA.
authors.forename: Jillian
authors.identifier: 0000-0002-3987-005X
authors.initials: J
authors.lastname: Frieder
authors.affiliation: Laboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA.
authors.forename: Kelsey
authors.identifier: 0000-0003-1385-4913
authors.initials: K
authors.lastname: Lawrence
authors.affiliation: Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Haynes
authors.affiliation: Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA ; Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA ; Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.
authors.forename: Malathy P V
authors.initials: MP
authors.lastname: Shekhar