title: Focal amplification of HOXD-harboring chromosome region is implicated in multiple-walled carbon nanotubes-induced carcinogenicity.
abstract: Multiple-walled carbon nanotubes (MWCNTs) may cause carcinogenesis. We found that long-term exposure to MWCNTs can induce irreversible oncogenic transformation of human bronchial epithelial cells and tumorigenicity in vivo. A genome-wide array-comparative genomic hybridization (aCGH) analysis revealed global chromosomal aberration in MWCNTs-treated clones, predominantly at chromosome 2q31-32, where the potential oncogenes HOXD9 and HOXD13 are located. Functional assays confirmed that this variation can modulate oncogenic signaling and plays a part in MWCNTs-induced tumorigenesis, suggesting that MWCNTs are carcinogens that act by altering genomic stability and oncogenic copy numbers.
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University , Taipei, Taiwan 112.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Shin-Sheng
authors.initials: SS
authors.lastname: Yuan
authors.forename: Chao-Chi
authors.initials: CC
authors.lastname: Ho
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Hsieh
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Hong
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Chin-Di
authors.initials: CD
authors.lastname: Wang
authors.forename: Ker-Chau
authors.initials: KC
authors.lastname: Li
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D063646:Carcinogenesis; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects* / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D015894:Genome, Human; D042822:Genomic Instability / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009363:Neoplasm Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C513184:HOXD13 protein, human; C088822:HOXD9 protein, human; D018398:Homeodomain Proteins; D037742:Nanotubes, Carbon; D009363:Neoplasm Proteins; D014157:Transcription Factors