title: Upregulation of ID2 antagonizes arsenic trioxide-induced antitumor effects in cancer cells.
abstract: OBJECTIVE
  Arsenic trioxide (ATO) strongly induces apoptosis and differentiation in acute promyelocytic leukemia, and induces cell cycle arrest in most solid tumors. Although many signaling pathways are involved in its antitumor mechanism, a detailed investigation of the transforming growth factor beta-bone morphogenetic protein signaling pathway has not been performed.
  
  
  METHODS
  A microarray containing 113 genes associated with the pathway was used to screen important molecules that participate in the antitumor effects of ATO. The expression levels of the inhibitors of DNA binding-2 (ID2) in 4 different types of cancer cells were determined by quantitative reverse transcription PCR and Western blotting. Human esophageal squamous cell carcinoma cell line Eca109 and pancreatic carcinoma cell line BxPC3 cells were transfected with siRNAs targeting ID2 and scrambled control siRNA. Cell proliferation was evaluated by methyl thiazolyl tetrazolium assay.
  
  
  RESULTS
  Eighteen upregulated and 12 downregulated genes were identified. After verification at the transcriptional and translational levels in 4 different cancer cells, ID2 was identified as an ATO antitumor-associated protein. In addition, specific silencing of ID2 could enhance ATO-induced cell proliferation inhibition in cancer cells.
  
  
  CONCLUSIONS
  A combination of ATO and ID2-targeted agents may have considerable therapeutic benefits in cancers.
authors: Xueyan
authors: X
authors: Zhang
authors: Chengqian
authors: C
authors: Lv
authors: Bing
authors: B
authors: Du
authors: Xiao
authors: X
authors: Ma
authors: Jingming
authors: J
authors: Guan
authors: Shanling
authors: S
authors: Gao
authors: Xiaodong
authors: X
authors: Li
authors: Lei
authors: L
authors: Zheng
authors: Lei
authors: L
authors: Lei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010087:Oxides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014176:Protein Biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D019485:Bone Morphogenetic Proteins; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D010087:Oxides; D016212:Transforming Growth Factor beta; D000077237:Arsenic Trioxide