Genetic analysis of indefinite division in human cells: Evidence for a cell senescence-related gene(s) on human chromosome 4

Yi Ning, James L. Weber, Ann M. Killary, David H. Ledbetter, James R. Smith, Olivia M. Pereira-Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Earlier studies had demonstrated that fusion of normal with immortal human cells yielded hybrids having limited division potential. This indicated that the phenotype of limited proliferation (cellular senescence) is dominant and that immortal cells result from recessive changes in normal growth-regulatory genes. In additional studies, we exploited the fact that the immortal phenotype is recessive and, by fusing various immortal human cell lines with each other, identified four complementation groups for indefinite division. Assignment of cell lines to specific groups allowed us to take a focused approach to identify the chromosomes and genes involved in growth regulation that have been modified in immortal cells. We report here that introduction of a normal human chromosome 4 into three immortal cell lines (HeLa, J82, T98G) assigned to complementation group B resulted in loss of proliferation and reversal of the immortal phenotype. No effect on the proliferation potential of cell lines representative of the other complementation groups was observed. This result suggests that a gene(s) involved in cellular senescence and normal growth regulation resides on chromosome 4.

Original languageEnglish (US)
Pages (from-to)5635-5639
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number13
DOIs
StatePublished - Jul 1 1991

Keywords

  • Aging
  • Cell immortalization
  • Cell proliferation
  • Microcell hybrids

ASJC Scopus subject areas

  • General

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