Renewed DNA synthesis in senescent WI‐38 cells by expression of an inducible chimeric c‐fos construct

Paul D. Phillips, Robert J. Pignolo, Kazuko Nishikura, Vincent J. Cristofalo

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

As normal human cells approach the end of their proliferative lifespan in vitro they lose responsiveness to a variety of growth factors, to which they respond with DNA replication when they are young. Recently it has been reported that the protooncogene c‐fos is not expressed in senescent cells (Seshadri and Campisi, 1990). In this study we have found that both c‐jun and jun B, partners of c‐fos in heterodimeric transactivating complexes, are equivalently expressed in young and senescent cells at both early (1–6 hr) and late (12 or 16 hr) time points following serum stimulation of quiescent cells. We have also investigated the effect of the enforced expression of c‐fos in senescent WI‐38 cells using an inducible construct carrying the murine c‐fos gene under the control of the sheep metallothionein promoter. We have found that the transient transfection and subsequent activation of the conditional promoter with Zn++ stimulated DNA synthesis in a significant fraction of senescent cells which had completed 90%–95% of their proliferative lifespan. However, populations which had completed 100% of their proliferative life span and nondividing cultures which had been selected with BrdU did not respond to the expression of the c‐fos gene. These results demonstrate that one of the primary events associated with senescence in human cells is the suppression of c‐fos gene expression, but additional phenotypic changes must also occur in order to explain the ultimate loss of proliferative responsiveness of these cells. © 1992 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)206-212
Number of pages7
JournalJournal of Cellular Physiology
Volume151
Issue number1
DOIs
StatePublished - Apr 1992

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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