Evidence for inactivation of distinct telomerase repressor genes in different types of human cancers

Hiromi Tanaka, Izumi Horikawa, J. Carl Barrett, Mitsuo Oshimura

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Telomerase activation, a critical event in human carcinogenesis, may result from defects in telomerase-repressing mechanisms. Data from microcell-mediated chromosome transfer (MMCT) suggests the presence of telomerase repressor genes that become inactivated during carcinogenic processes. The transfer of a normal human chromosome 3 represses telomerase activity of both human renal cell carcinoma (RCC) and breast carcinoma (BC) cells. For a genetic complementation analysis of telomerase repression, 2 RCC cell lines (KC12 and RCC23) and a BC cell line (21NT) were used to make somatic cell hybrids. All of the self-hybrids (KC12xKC12 and 21NTx21NT) and hybrids from 2 RCC cell lines (KC12xRCC23) expressed the telomerase activity similarly to their parental cells, excluding the possibility of a ploidy-associated change in telomerase activity and suggesting the same genetic defect shared by the 2 RCC cell lines. In contrast, the fusion of BC and RCC cells (21NTxKC12 and 21NTxRCC23) produced a significant number of telomerase-negative hybrids, suggesting that the RCC and BC cells have different defects in the telomerase repression, which are functionally corrected through genetic complementation in the hybrids. This notion was supported by the mapping of the RCC telomerase repressor gene to a 5.7-Mb region on 3p21, which is different from the candidate region for the BC telomerase repressor gene on the same chromosomal band. These findings provide direct evidence for inactivation of distinct telomerase repressor genes in different types of human cancers and may have implications in the tissue-specific regulation of telomerase during human development and carcinogenesis.

Original languageEnglish (US)
Pages (from-to)653-657
Number of pages5
JournalInternational Journal of Cancer
Volume115
Issue number4
DOIs
StatePublished - Jul 1 2005

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Keywords

  • Cellular senescence
  • Chromosome transfer
  • Somatic cell hybrids
  • Telomerase repressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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