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

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...

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Main Authors: Karli Rosner, Darius R. Mehregan, Evangelia Kirou, Judith Abrams, Seongho Kim, Michelle Campbell, Jillian Frieder, Kelsey Lawrence, Brittany Haynes, Malathy P. V. Shekhar
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Skin Cancer
Online Access:http://dx.doi.org/10.1155/2014/439205
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author Karli Rosner
Darius R. Mehregan
Evangelia Kirou
Judith Abrams
Seongho Kim
Michelle Campbell
Jillian Frieder
Kelsey Lawrence
Brittany Haynes
Malathy P. V. Shekhar
author_facet Karli Rosner
Darius R. Mehregan
Evangelia Kirou
Judith Abrams
Seongho Kim
Michelle Campbell
Jillian Frieder
Kelsey Lawrence
Brittany Haynes
Malathy P. V. Shekhar
author_sort Karli Rosner
collection DOAJ
description 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.
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spelling doaj-art-3e8e0e8a89144ea8b298fd4c23248a5a2025-02-03T01:31:34ZengWileyJournal of Skin Cancer2090-29052090-29132014-01-01201410.1155/2014/439205439205Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell MembraneKarli Rosner0Darius R. Mehregan1Evangelia Kirou2Judith Abrams3Seongho Kim4Michelle Campbell5Jillian Frieder6Kelsey Lawrence7Brittany Haynes8Malathy P. V. Shekhar9Laboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USADepartment of Dermatology, School of Medicine, Wayne State University, Detroit, MI 48201, USALaboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USABiostatistics, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USABiostatistics, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USAPinkus Dermatopathology Laboratory, Monroe, MI 48162, USALaboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USALaboratory for Molecular Dermatology, Barbara Ann Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USADepartment of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USAWe 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.http://dx.doi.org/10.1155/2014/439205
spellingShingle Karli Rosner
Darius R. Mehregan
Evangelia Kirou
Judith Abrams
Seongho Kim
Michelle Campbell
Jillian Frieder
Kelsey Lawrence
Brittany Haynes
Malathy P. V. Shekhar
Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell Membrane
Journal of Skin Cancer
title Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell Membrane
title_full Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell Membrane
title_fullStr Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell Membrane
title_full_unstemmed Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell Membrane
title_short Melanoma Development and Progression Are Associated with Rad6 Upregulation and β-Catenin Relocation to the Cell Membrane
title_sort melanoma development and progression are associated with rad6 upregulation and β catenin relocation to the cell membrane
url http://dx.doi.org/10.1155/2014/439205
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