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Cancer letters
Feb 01, 2014;343 (1): 14-23.

Non-small cell lung cancer is susceptible to induction of DNA damage responses and inhibition of angiogenesis by telomere overhang oligonucleotides.

Neelu Puri, Ryan T Pitman, Richard E Mulnix, Terrianne Erickson, Audra N Iness, Connie Vitali, Yutong Zhao, Ravi Salgia
Author Information
  1. Neelu Puri: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States. Electronic address: neelupur@uic.edu.
  2. Ryan T Pitman: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
  3. Richard E Mulnix: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
  4. Terrianne Erickson: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
  5. Audra N Iness: Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, IL, United States.
  6. Connie Vitali: Department of Pathology, University of Illinois College of Medicine, Rockford, IL, United States.
  7. Yutong Zhao: Department of Medicine, Division of Pulmonary, Allergy, Critical Care, University of Pittsburgh, Pittsburgh, PA, United States.
  8. Ravi Salgia: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, United States.
PMID: 24041868 DOI: 10.1016/j.canlet.2013.09.010

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.

Keywords

Angiogenesis Apoptosis Lung cancer Senescence Telomere overhang p53

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Grants

  1. R01 HL091916/NHLBI NIH HHS
  2. R01 HL112791/NHLBI NIH HHS

MeSH Term

Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Bronchi
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Cell Proliferation
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
DNA Damage
Epithelial Cells
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Humans
Inhibitor of Growth Protein 1
Intracellular Signaling Peptides and Proteins
Male
Mice
Mice, Nude
Neoplasm Transplantation
Neovascularization, Pathologic
Nuclear Proteins
Oligonucleotides
Signal Transduction
Telomere
Tumor Suppressor Proteins
Vascular Endothelial Growth Factor A

Chemicals

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
ING1 protein, human
Inhibitor of Growth Protein 1
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Oligonucleotides
SPZ1 protein, human
Tumor Suppressor Proteins
VEGFA protein, human
Vascular Endothelial Growth Factor A
Cyclin-Dependent Kinase Inhibitor p27
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 3

Word Cloud

Created with Highcharts 10.0.0overhangcellcancertelomereDNAdamageT-oligosenescencelungNSCLCcellsp53inductionexpressionangiogenesisExposureactssignalexogenousadministration11-baseoligonucleotidehomologous3'-telomeresequencemimicseffectsexposureinducingdeathnon-smallnormalbronchialepithelialT-oligo-induceddecreasecellularproliferationlikelydirectedhomologp73subsequentsenescence-associatedproteinsp21p33INGp27Kip1vivovitroAdditionallydecreasestumorsizeinhibitsdecreasedVEGFsignalingincreasedTSP-1Non-smallsusceptibleresponsesinhibitionoligonucleotidesAngiogenesisApoptosisLungSenescenceTelomere

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