title: Epigenetic marks responsible for cadmium-induced melanoma cell  overgrowth.
abstract: Cadmium (Cd) is a human carcinogen that likely acts via epigenetic mechanisms. However, the precise role of Cd in melanoma remains to be defined. The goals of this study are to: (i) examine the effect of Cd on the proliferation rate of cutaneous and uveal melanoma cells; (ii) identify the genes affected by Cd exposure; (iii) understand whether epigenetic changes are involved in the response to Cd. The cell growth capacity increased at 48 h after Cd treatment at doses ranging from 0.5 to 10 μM. The research on the key genes regulating proliferation has shown that aberrant methylation is responsible for silencing of p16(INK4A) and caspase 8 in uveal and cutaneous melanoma cells, respectively. The methylation and expression patterns of p14(ARF), death receptors 4/5, and E-cadherin remained unmodified after Cd treatment in all the cell lines analyzed. Ectopic expression of p16(INK4A) abolished the overgrowth of uveal melanoma cells in response to Cd and the overexpression of caspase 8 drastically increased the apoptotic rate of Cd-treated cutaneous melanoma cells. In conclusion, our data suggest that hypermethylation of p16(INK4A) and caspase 8 represents the most common event linked to Cd-induced stimulation of cell growth and inhibition of cell death pathway in melanoma.
authors.affiliation: Department of Experimental Specialized Medical and Surgical and Odontostomatology Sciences, University of Messina, Messina, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Venza
authors.forename: Maria
authors.initials: M
authors.lastname: Visalli
authors.forename: Carmelo
authors.initials: C
authors.lastname: Biondo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Oteri
authors.forename: Federica
authors.initials: F
authors.lastname: Agliano
authors.forename: Silvia
authors.initials: S
authors.lastname: Morabito
authors.forename: Diana
authors.initials: D
authors.lastname: Teti
authors.forename: Isabella
authors.initials: I
authors.lastname: Venza
mesh_terms: D019256:Cadmium Chloride / Q000633:toxicity*; D053181:Caspase 8 / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006801:Humans; D008545:Melanoma / Q000139:chemically induced*; D008745:Methylation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced; D025803:Tumor Suppressor Protein p14ARF / Q000187:drug effects; D014604:Uveal Neoplasms / Q000139:chemically induced
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C114109:TNFRSF21 protein, human; D025803:Tumor Suppressor Protein p14ARF; D053181:Caspase 8; D019256:Cadmium Chloride