title: Non-small cell lung cancer is susceptible to induction of DNA damage responses and inhibition of angiogenesis by telomere overhang oligonucleotides.
abstract: Exposure of the telomere overhang acts as a DNA damage signal, and exogenous administration of an 11-base oligonucleotide homologous to the 3'-telomere overhang sequence (T-oligo) mimics the effects of overhang exposure by inducing senescence and cell death in non-small cell lung cancer (NSCLC) cells, but not in normal bronchial epithelial cells. T-oligo-induced decrease in cellular proliferation in NSCLC is likely directed through both p53 and its homolog, p73, with subsequent induction of senescence and expression of senescence-associated proteins, p21, p33(ING), and p27(Kip1) both in vivo and in vitro. Additionally, T-oligo decreases tumor size and inhibits angiogenesis through decreased VEGF signaling and increased TSP-1 expression.
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States. Electronic address: neelupur@uic.edu.
authors.forename: Neelu
authors.initials: N
authors.lastname: Puri
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Pitman
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Mulnix
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
authors.forename: Terrianne
authors.initials: T
authors.lastname: Erickson
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
authors.forename: Audra N
authors.initials: AN
authors.lastname: Iness
authors.affiliation: Department of Pathology, University of Illinois College of Medicine, Rockford, IL, United States.
authors.forename: Connie
authors.initials: C
authors.lastname: Vitali
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, Critical Care, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, United States.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D001980:Bronchi / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004249:DNA Damage; D004847:Epithelial Cells / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics; D015398:Signal Transduction; D016615:Telomere / Q000648:ultrastructure*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D009841:Oligonucleotides; C481348:SPZ1 protein, human; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Angiogenesis; Apoptosis; Lung cancer; Senescence; Telomere overhang; p53
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