title: Metallothionein isoform 3 expression in human skin, related cancers and human skin derived cell cultures.
abstract: Human skin is a well known target site of inorganic arsenic with effects ranging from hyperkeratosis to dermal malignancies. The current study characterizes the expression of a protein known to bind inorganic, As(3+), metallothionein 3 (MT-3). Expression of this protein was assessed immunohistochemically with a specific MT-3 antibody on human formalin-fixed, paraffin-embedded biopsy specimens in normal skin, squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. Assessment in normal skin using nine normal specimens showed moderate to intense MT-3 staining in epidermal karatinocytes with staining extending into the basal cells and moderate to intense staining in melanocytes of nevi. MT-3 immunoexpression was shown to be moderate to intense in 12 of 13 of SCC, low to moderate in 8 of 10 BCC, and moderate to intense in 12 melanoma samples. MT-3 expression in cell culture models (normal human epidermal keratinocytes, normal human melanocytes, and HaCaT cells) showed only trace expression of MT-3, while exposures to the histone deacytalase inhibitor, MS-275, partially restored expression levels. These results indicate that the epidermis of human skin and resulting malignancies express high level of MT-3 and potentially impact on the known association of arsenic exposure and the development of skin disorders and related cancers.
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: andrea.slusser@med.und.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Slusser
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: yun.zheng@med.und.edu.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: xudong.zhou@med.und.edu.
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Zhou
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: seema.somji@med.und.edu.
authors.forename: Seema
authors.initials: S
authors.lastname: Somji
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: donald.sens@med.und.edu.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Sens
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: mary.sens@med.und.edu.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Sens
authors.affiliation: Department of Pathology School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202, United States. Electronic address: scott.garrett@med.und.edu.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Garrett
mesh_terms: D001152:Arsenicals / Q000378:metabolism; D001706:Biopsy; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016022:Case-Control Studies; D002460:Cell Line; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D001152:Arsenicals; D056572:Histone Deacetylase Inhibitors; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins