Helicobactor pylori Infection Is Closely Associated with Telomere Reduction in Gastric Mucosa

Objective: To investigate differential reduction in telomere DNA in tissue components of gastric mucosa with respect to Helicobactor pylori infection. Materials and Methods: The telomere content was examined by fluorescent in situ hybridization with the (TTAGGG)4 probe. To compare the signal intensities from the probe (telomere volume) with telomere length, five gastric carcinoma cell lines were used. Telomere volumes were examined in 9 healthy persons, 124 non-cancer patients, and 86 gastric cancer patients. Results: Telomere volume showed a linear correlation with telomere length measured by Southern blotting in gastric carcinoma cells. In healthy persons without H. pylori infection, the telomere volumes of gastric epithelial tissues were 70–79% that of intramucosal lymphocytes (internal control). In 124 patients without gastric cancer, telomere volume of H.-pylori-infected mucosa was significantly less than that of H.-pylori-negative mucosa in both metaplastic and non- metaplastic tissues (p < 0.0001). In 86 gastric cancer patients, telomere volumes in intestinal metaplasia adjacent to cancer were 75% that of intestinal metaplasia of non-cancer patients (p = 0.0001). hTERT expression was detected in 6 cancer-associated and 2 cancer-negative intestinal metaplasia specimens, in which telomere volume was markedly reduced. Conclusion:H. pylori infection is closely associated with telomere reduction in gastric epithelium.

[1]  A. Mitchell DNA replication: A time for silence , 2002, Nature Reviews Molecular Cell Biology.

[2]  David Tosh,et al.  How cells change their phenotype , 2002, Nature Reviews Molecular Cell Biology.

[3]  K. Chayama,et al.  Expression of telomeric repeat binding factor 1 and 2 and TRF1-interacting nuclear protein 2 in human gastric carcinomas. , 2001, International journal of oncology.

[4]  G. Testino Helicobacter pylori, cell proliferation, and carcinogenesis. , 2001, The American journal of gastroenterology.

[5]  V. Rus,et al.  Telomeres, telomerase, and lupus: the long and short of it. , 2001, Clinical immunology.

[6]  B. Braden,et al.  Detection of Helicobacter pylori infection: when to perform which test? , 2001, Annals of medicine.

[7]  D. Kobayashi,et al.  Helicobacter pylori Infection: Augmentation of Telomerase Activity in Cancer and Noncancerous Tissues , 2000, World Journal of Surgery.

[8]  S. Futagawa,et al.  Effect of Age on the Relationship between Gastric Cancer and Helicobacter pylori , 2000, Japanese journal of cancer research : Gann.

[9]  K. Takubo,et al.  Telomere shortening in gastric carcinoma with aging despite telomerase activation , 2000, Journal of Cancer Research and Clinical Oncology.

[10]  C. Bucana,et al.  Relative expression of type IV collagenase, E-cadherin, and vascular endothelial growth factor/vascular permeability factor in prostatectomy specimens distinguishes organ-confined from pathologically advanced prostate cancers. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[11]  H. Yokozaki,et al.  Helicobactor pylori infection and carcinogenesis of the stomach , 2000, Langenbeck's Archives of Surgery.

[12]  J. Fujimoto,et al.  Genetic and epigenetic alterations in multistep carcinogenesis of the stomach. , 2000, Journal of gastroenterology.

[13]  K. Luettich,et al.  Improved in situ detection method for telomeric tandem repeats in metaphase spreads and interphase nuclei , 2000, Molecular pathology : MP.

[14]  F. Collins,et al.  Design of modified oligodeoxyribonucleotide probes to detect telomere repeat sequences in FISH assays. , 1999, Nucleic acids research.

[15]  Y. Bang,et al.  Up‐regulation of human telomerase catalytic subunit during gastric carcinogenesis , 1999, Cancer.

[16]  J. Fujimoto,et al.  Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections , 1999, Oncogene.

[17]  K. Naka,et al.  Effect of antisense human telomerase RNA transfection on the growth of human gastric cancer cell lines. , 1999, Biochemical and biophysical research communications.

[18]  R. Weinberg,et al.  Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase , 1998, Oncogene.

[19]  B. Levine,et al.  Tales of tails: regulation of telomere length and telomerase activity during lymphocyte development, differentiation, activation, and aging , 1997, Immunological reviews.

[20]  J. Soria,et al.  [Telomeres, telomerase and cancer]. , 1997, Bulletin du cancer.

[21]  L. Laine,et al.  Prospective comparison of H&E, Giemsa, and Genta stains for the diagnosis of Helicobacter pylori. , 1997, Gastrointestinal endoscopy.

[22]  J. Shay,et al.  Multiple pathways for the regulation of telomerase activity. , 1997, European journal of cancer.

[23]  H. Yokozaki,et al.  Expression of Human Telomerase RNA Is an Early Event of Stomach Carcinogenesis , 1997, Japanese journal of cancer research : Gann.

[24]  B. van Steensel,et al.  Structure, subnuclear distribution, and nuclear matrix association of the mammalian telomeric complex , 1996, The Journal of cell biology.

[25]  Holmberg Sb Premalignant lesions of the stomach. , 1996 .

[26]  J. Shay,et al.  Telomerase activity in gastric cancer. , 1995, Cancer research.

[27]  J. Shay,et al.  Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas. , 1995, Cancer research.

[28]  V. French,et al.  The long and the short of it , 1993, Nature.

[29]  P. Franck,et al.  Flow cytometric analysis of the cell cycle in chronic gastritis. , 1992, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[30]  D. Tse,et al.  Architectural organization in the interphase nucleus of the protozoan Trypanosoma brucei: location of telomeres and mini‐chromosomes. , 1990, The EMBO journal.

[31]  M. Blaser Gastric Campylobacter-like organisms, gastritis, and peptic ulcer disease. , 1987, Gastroenterology.

[32]  P. Gedigk,et al.  Premalignant lesions of the stomach. , 1979, Israel journal of medical sciences.

[33]  L. Ellis,et al.  Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[34]  F. Ishikawa,et al.  Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas , 1998, Nature Genetics.

[35]  S. Hirohashi,et al.  Genetic Alterations in the Precursors of Gastric Cancer , 1997 .

[36]  C. Greider,et al.  Telomere length regulation. , 1996, Annual review of biochemistry.

[37]  胃癌研究会 Japanese classification of gastric carcinoma , 1995 .

[38]  Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994. , 1994, IARC monographs on the evaluation of carcinogenic risks to humans.

[39]  H. Cooke,et al.  In vivo loss of telomeric repeats with age in humans. , 1991, Mutation research.

[40]  N. Kamada,et al.  Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c-myc oncogene. , 1991, Cancer research.