Telomerase-independent senescence of human immortal cells induced by microcell-mediated chromosome transfer

Hiromi Tanaka, Izumi Horikawa, Hiroyuki Kugoh, Motoyuki Shimizu, J. Carl Barrett, Mitsuo Oshimura

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Maintenance of telomeres, commonly through expression of telomerase activity, is necessary but may not be sufficient for human cells to escape from the cellular senescence program and become immortal. We report here that human tumor cells could undergo cellular senescence in the presence of telomerase activity when a specific normal human chromosome was introduced via microcell-mediated chromosome transfer. The cell models studied include SiHa (uterine cervical carcinoma cells expressing E6 and E7 oncoproteins of human papillomavirus type 16) with a transferred chromosome 2, CC1 (choriocarcinoma cells expressing an amino-terminally truncated p53 protein) with a transferred chromosome 7, and JTC-32 (bladder carcinoma cells) with a transferred chromosome 11. The microcell hybrids with the indicated chromosomes ceased to divide after five to 10 population doublings and showed senescence-associated β-galactosidase activity but still expressed the genes encoding three components of human telomerase, consistent with the retention of telomerase activity. These results are evidence for barriers to human cell immortalization, which involve activation of unidentified senescence-inducing genes that function independently of inactivation of telomerase.

Original languageEnglish (US)
Pages (from-to)249-255
Number of pages7
JournalMolecular Carcinogenesis
Volume25
Issue number4
DOIs
StatePublished - Aug 17 1999

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Keywords

  • Chromosome transfer
  • Senescence
  • Telomerase
  • Telomere
  • Tumor cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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