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  • Original Paper
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Functional evidence for a telomerase repressor gene on human chromosome 10p15.1

Oncogene volume 20, pages 828–835 (2001)Cite this article

Abstract

Based on the sites of frequent allelic loss in hepatocellular carcinoma, five normal human chromosomes (2, 4, 5, 10 and 16) were transferred individually into a telomerase-positive human hepatocellular carcinoma cell line, Li7HM, by microcell-mediated chromosome transfer (MMCT). Chromosome 10, but not the others, repressed telomerase activity immediately and stopped cell growth after 50 population doublings (PDs). Loss of the transferred 10p loci resulted in the emergence of revertant cells that continued to proliferate and expressed telomerase activity, suggesting the presence of a telomerase repressor gene on this chromosomal arm. Transfer of a series of defined fragments from chromosome 10p successfully narrowed down the responsible region: a 28.9-cM region on 10p15 (between WI-4752 and D10S249), but not a 26.2-cM region (between D10S1728 and D10S249), caused repression of telomerase activity and progressive telomere shortening. A strong correlation between the expression level of telomerase catalytic subunit gene (hTERT) and telomerase activity was observed. These findings suggest that a novel telomerase repressor gene which controls the expression of hTERT is located on the 2.7-cM region (between WI-4752 and D10S1728) on chromosome 10p15.1.

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Acknowledgements

We thank Dr T Shulz for valuable comments and suggestions. This work was supported in part by a Grant-in Aid for the Second Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.

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Author notes

  1. Arata Nishimoto and Norimasa Miura: A Nishimoto and N Miura contributed equally to this work

Authors and Affiliations

  1. Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, 683-8503, Tottori, Japan

    Arata Nishimoto, Norimasa Miura, Hiroyuki Kugoh & Mitsuo Oshimura

  2. Laboratory of Biosystems and Cancer, Cancer and Aging Section, National Cancer Institute, Bethesda, MD 20892-2440, Maryland, USA

    Izumi Horikawa & J Carl Barrett

  3. Tumor Suppression and Functional Genomics Project, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yoshinori Murakami

  4. Pathology Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Setsuo Hirohashi

  5. The Second Department of Internal Medicine, Tottori University, Yonago, 683-8503, Tottori, Japan

    Hironaka Kawasaki

  6. Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, Texas, USA

    Adi F Gazdar

  7. Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, Texas, USA

    Jerry W Shay

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  1. Arata Nishimoto
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Nishimoto, A., Miura, N., Horikawa, I. et al. Functional evidence for a telomerase repressor gene on human chromosome 10p15.1. Oncogene 20, 828–835 (2001). https://doi.org/10.1038/sj.onc.1204165

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