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. 2018 Apr;15(4):5161-5166.
doi: 10.3892/ol.2018.7927. Epub 2018 Feb 2.

Effects of TIN2 on telomeres and chromosomes in the human gastric epithelial cell line GES-1

Fan Fu  1   2 , Hua Hu  3 , Shuai Yang  4 , Xiaoqiu Liang  1
Affiliations

Effects of TIN2 on telomeres and chromosomes in the human gastric epithelial cell line GES-1

Fan Fu et al. Oncol Lett. 2018 Apr.

Abstract

TERF1-interacting nuclear factor 2 (TIN2) is a key member of the protein complexes that protect telomeres. TIN2 contributes an important role in biological processes. In a previous study by the present authors, an association was reported between high TIN2 protein expression and gastric cancer. Therefore, it was hypothesized that abnormal TIN2 expression may cause the development of malignancies, including, gastric carcinomas. To investigate this hypothesis, the present study employed peptide nucleic acid fluorescence in situ hybridization technology to analyze the human gastric epithelial GES-1 cells with high TIN2 expression or inhibited TIN2 expression. The results indicated that GES-1 cell lines with high TIN2 expression exhibited greater telomere dysfunction-induced damage compared with GES-1 cell lines with inhibited TIN2 expression. Chromosome analysis indicated that GES-1 cells with high TIN2 expression exhibited 2.48±1.30 aberrant chromosomal changes per 100 cells, that may contribute to telomere DNA damage. Therefore, aberrant chromosomal alterations may provide a novel perspective for the pathogenesis of gastric cancer.

Keywords: GES-1 cells; TERF1-interacting nuclear factor 2; chromosome aberration; telomere dysfunction induced-foci.

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Figures

Figure 1.
Figure 1.
Relative expression levels of TIN2 in GES-1 and corresponding transfected cell lines. *P<0.05 vs. GES-1 cells. GES-1, normal human gastric epithelial cell line; GES-1-GFP, TIN2 overexpression vector group; GES-1-hTIN2, TIN2 overexpression group; GES-1-GTP-NC, low TIN2 expression vector group; GES-1-hTIN2-SH3, inhibited TIN2 expression group; TIN2, TERF1-interacting nuclear factor 2.
Figure 2.
Figure 2.
Detection of TIN2 protein expression in GES-1 and corresponding transfected cells lines by western blotting. *P<0.05 vs. GES-1 cells. GES-1-hTIN2-SH3, inhibited TIN2 expression group; GES-1-GTP-NC, low TIN2 expression vector group; NC, negative control; TIN2, TERF1-interacting nuclear factor 2.
Figure 3.
Figure 3.
PNA-fluorescence in situ hybridization analysis of TIF formation. (A) Fluorescent staining of nuclei (blue), H2AX (green) and PNA (red). An increased number of TIFs were detected in the TIN2 high expression group compared with the group with inhibited TIN2 expression. TIFs were not detected in the other groups. (B) Percentage of cells with >2 TIFs in GES-1 and corresponding transfected cells lines. *P<0.05 vs. GES-1, GES-1-GFP and GES-1-GTP-NC. #P<0.05 vs. GES-1-hTIN2-SH3. Magnification, ×1,000. GES-1, normal human gastric epithelial cell line; GES-1-GFP, TIN2 overexpression vector group; GES-1-hTIN2, TIN2 overexpression group; GES-1-GTP-NC, low TIN2 expression vector group; GES-1-hTIN2-SH3, inhibited TIN2 expression group; PNA, peptide nucleic acid; TIF, telomere dysfunction induced-foci; TIN2, TERF1-interacting nuclear factor 2.
Figure 4.
Figure 4.
Chromosome morphology in (A) GES-1-hTIN2, (B) GES-1-GTP, (C) GES-1-hTIN2-SH3, (D) GES-1-GTP-NC and (E) GES-1 cells. The arrows indicate chromosomal aberrations. Chromosomal aberrations are detected in the GES-1-hTIN2 and GES-1-hTIN2-SH3 groups. Furthermore, the GES-1-hTIN2 group demonstrated more circular chromosome structures and chromosome end fusions, compared with the GES-1-hTIN2-SH3 group. Magnification, ×1,000. GES-1-hTIN2, TIN2 overexpression group; GES-1-hTIN2-SH3, inhibited TIN2 expression group; GES-1-GTP-NC, low TIN2 expression vector group; GES-1-GFP, TIN2 overexpression vector group.
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References

    1. Bruedigam C, Lane SW. Telomerase in hematologic malignancies. Curr Opin Hematol. 2016;23:346–353. doi: 10.1097/MOH.0000000000000252. - DOI - PubMed
    1. de Lange T. Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–2110. doi: 10.1101/gad.1346005. - DOI - PubMed
    1. O'Sullivan RJ, Karlseder J. Telomeres: Protecting chromosomes against genome instability. Nat Rev Mol Cell Biol. 2010;11:171–181. doi: 10.1038/nrm2848. - DOI - PMC - PubMed
    1. Frescas D, de Lange T. A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice. Genes Dev. 2014;28:153–166. doi: 10.1101/gad.233395.113. - DOI - PMC - PubMed
    1. Frescas D, de Lange T. Binding of TPP1 protein to TIN2 protein is required for POT1a,b protein-mediated telomere protection. J Biol Chem. 2014;289:24180–24187. doi: 10.1074/jbc.M114.592592. - DOI - PMC - PubMed