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Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma

Oncogene volume 24, pages 157–164 (2005)Cite this article

Abstract

The expression of PINX1, a possible telomerase inhibitor and a putative tumor suppressor, has not been studied in human cancers, including gastric cancer (GC). We examined expression of PINX1 by quantitative reverse transcription (RT)–PCR in 73 cases of GC, and 45 of these cases were further studied for loss of heterozygosity (LOH) by PCR with microsatellite marker D8S277. Reduced expression (tumor vs normal ratio<0.5) of PINX1 was detected in 50 (68.5%) of 73 cases of GC. GC tissues with reduced expression of PINX1 showed significantly higher telomerase activities as measured by telomeric repeat amplification protocol than those with normal expression of PINX1 (P = 0.031). LOH of PINX1 locus was detected in 15 (33.3%) of 45 cases of GC and was correlated significantly with reduced expression of PINX1 (P=0.031). Expression of PINX1 in a GC cell line, MKN-74, was induced by treatment with trichostatin A (TSA) or nicotinamide (NAM). Chromatin immunoprecipitation assay of MKN-74 cells revealed that acetylation of histone H4 in the 5′ untranslated region (UTR) of PINX1 was enhanced by treatment with TSA or NAM, whereas acetylation of histone H3 was not changed by TSA or NAM. In addition, TSA or NAM treatment led to inhibition of telomerase activity in MKN-74 cells. These results indicate that LOH of PINX1 locus and hypoacetylation of histone H4 in the 5′ UTR of PINX1 are associated with reduced expression of PINX1 in GC.

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Acknowledgements

We thank Mr M Takatani and Ms M Ueda for their excellent technical assistance and advice.

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Authors and Affiliations

  1. Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Tomohiro Kondo, Naohide Oue, Yoshitsugu Mitani, Kazuya Kuraoka, Hirofumi Nakayama & Wataru Yasui

  2. Department of Molecular Pathology, Nara Medical University, Kashihara, Japan

    Hiroki Kuniyasu

  3. Department of Oncological Science (Surgery II), Oita University Faculty of Medicine, Oita, Japan

    Tsuyoshi Noguchi

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  1. Tomohiro Kondo
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  2. Naohide Oue
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  7. Hirofumi Nakayama
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Correspondence to Wataru Yasui.

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Kondo, T., Oue, N., Mitani, Y. et al. Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma. Oncogene 24, 157–164 (2005). https://doi.org/10.1038/sj.onc.1207832

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