title: Ataxia-telangiectasia group D complementing gene (ATDC) promotes lung cancer cell proliferation by activating NF-κB pathway.
abstract: Previous studies suggested Ataxia-telangiectasia group D complementing gene (ATDC) as an oncogene in many types of cancer. However, its expression and biological functions in non-small cell lung cancer (NSCLC) remain unclear. Herein, we investigated its expression pattern in 109 cases of human NSCLC samples by immunohistochemistry and found that ATDC was overexpressed in 62 of 109 NSCLC samples (56.88%). ATDC overexpression correlated with histological type (p<0.0001), tumor status (p = 0.0227) and histological differentiation (p = 0.0002). Next, we overexpressed ATDC in normal human bronchial epithelial cell line HBE and depleted its expression in NSCLC cell lines A549 and H1299. MTT and colony formation assay showed that ATDC overexpression promoted cell proliferation while its depletion inhibited cell growth. Furthermore, cell cycle analysis showed that ATDC overexpression decreased the percentage of cells in G1 phase and increased the percentage of cells in S phase, while ATDC siRNA treatment increased the G1 phase percentage and decreased the S phase percentage. Further study revealed that ATDC overexpression could up-regulate cyclin D1 and c-Myc expression in HBE cells while its depletion down-regulated cyclin D1 and c-Myc expression in A549 and H1299 cells. In addition, ATDC overexpression was also associated with an increased proliferation index, cyclin D1 and c-Myc expression in human NSCLC samples. Further experiments demonstrated that ATDC up-regulated cyclin D1 and c-Myc expression independent of wnt/β-catenin or p53 signaling pathway. Interestingly, ATDC overexpression increased NF-κB reporter luciferase activity and p-IκB protein level. Correspondingly, NF-κB inhibitor blocked the effect of ATDC on up-regulation of cyclin D1 and c-Myc. In conclusion, we demonstrated that ATDC could promote lung cancer proliferation through NF-κB induced up-regulation of cyclin D1 and c-Myc.
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang City, China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Tang
authors.forename: Qian-Ze
authors.initials: QZ
authors.lastname: Dong
authors.forename: Quan-Zhe
authors.initials: QZ
authors.lastname: Cui
authors.forename: Paulie
authors.initials: P
authors.lastname: Papavassiliou
authors.forename: En-Di
authors.initials: ED
authors.lastname: Wang
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000503:physiopathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002681:China; D019938:Cyclin D1 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D016328:NF-kappa B / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C087296:TRIM29 protein, human; D014157:Transcription Factors; D019938:Cyclin D1; D008156:Luciferases