title: Evaluation of tubulin β-3 as a novel senescence-associated gene in melanocytic malignant transformation.
abstract: Malignant melanoma might develop from melanocytic nevi in which the growth-arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth-arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β-3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies. Depletion of tubulin β-3 caused accumulation of cells in the G2/M phase and decreased proliferation and migration. Immunohistochemical assessment of tubulin β-3 in benign lesions revealed strong staining in the superficial part of the intradermal components, which faded with depth. In contrast, primary melanomas exhibited staining without gradient in a disordered pattern and strong staining of the invasive front. Our results describe an approach to find clinically useful diagnostic biomarkers to more precisely identify cutaneous malignant melanoma and present tubulin β-3 as a candidate marker.
authors.affiliation: Department of Dermatology and Venereology, Linköping University, Linköping, Sweden.|Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Orfanidis
authors.affiliation: Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Wäster
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Department of Clinical Pathology and Clinical Genetics, Linköping University, Linköping, Sweden.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lundmark
authors.affiliation: Department of Dermatology and Venereology, Linköping University, Linköping, Sweden.|Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Rosdahl
authors.affiliation: Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Karin
authors.identifier: 0000-0003-4075-159X
authors.initials: K
authors.lastname: Öllinger
mesh_terms: D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009508:Nevus, Pigmented / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: C498585:TUBB3 protein, human; D014404:Tubulin
keywords: melanoma; microarray; nevus; senescence; tubulin β-3