title: Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation.
abstract: Both nickel and cadmium compounds have been established as group I carcinogens for several decades. Despite over-whelming evidence of these compounds' carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal induced cellular transformation remain unclear. In this study, we found that there were slightly different effects on decreased SLBP mRNA and protein as well as increased polyA H3.1 in our nickel exposed cells. This suggested that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. We also saw that the depletion of SLBP protein was reversed by inhibiting the proteosome. Finally, we showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel's effects on SLBP may be mediated via epigenetic mechanisms. Taken together these results suggest a similar mechanism by which both arsenic and nickel may exert their carcinogenic effects.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Ashley
authors.initials: A
authors.lastname: Jordan
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan, Hubei, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.
authors.forename: Freda
authors.initials: F
authors.lastname: Laulicht-Glick
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America.
authors.forename: Max
authors.identifier: http://orcid.org/0000-0003-0000-3028
authors.initials: M
authors.lastname: Costa
mesh_terms: D002104:Cadmium / Q000494:pharmacology*; D002460:Cell Line; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009532:Nickel / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D012333:RNA, Messenger; C092663:SLBP protein, human; D039221:mRNA Cleavage and Polyadenylation Factors; D002104:Cadmium; D009532:Nickel