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

Arata Nishimoto, Norimasa Miura, Izumi Horikawa, Hiroyuki Kugoh, Yoshinori Murakami, Setsuo Hirohashi, Hironaka Kawasaki, Adi F. Gazdar, Jerry W. Shay, J. Carl Barrett, Mitsuo Oshimura

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)828-835
Number of pages8
JournalOncogene
Volume20
Issue number7
DOIs
StatePublished - Feb 15 2001

Keywords

  • Chromosome 10p
  • Microcell-mediated chromosome transfer
  • Telomerase
  • Telomerase repressor gene
  • hTERT

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Nishimoto, A., Miura, N., Horikawa, I., Kugoh, H., Murakami, Y., Hirohashi, S., Kawasaki, H., Gazdar, A. F., Shay, J. W., Barrett, J. C., & Oshimura, M. (2001). Functional evidence for a telomerase repressor gene on human chromosome 10p15.1. Oncogene, 20(7), 828-835. https://doi.org/10.1038/sj.onc.1204165