title: Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1.
abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Carpenter
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jing
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*
chemical_list: D018053:Arsenites; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C015001:arsenite