Cyclin A levels, the duration of S phase and sensitivity to a chemotherapeutic agent are altered in fibroblasts cultured on a fibronectin matrix

Insung Min, Matthew C. Stubbs, Gordon D. Strachan, David J. Hall

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Culture of murine embryonic fibroblasts, but not vascular smooth muscle cells, on a fibronectin matrix significantly shortens their transit time through the S phase of the cell cycle. This shortening corresponds to an increase in both cyclin A protein levels and active cyclin A/cdk2 complex. The increase in cyclin A protein appears due to a translational/post- translational mechanism since there is no increase in cyclin A mRNA following culture of the cells on fibronectin. Treatment of cells cultured on fibronectin with a short pulse of the S phase chemotherapeutic agent camptothecin, resulted in a relative protection from cell death when compared to cells cultured on tissue culture plastic. Thus, while the cells have increased rate of transit through S phase fibronectin-mediated signaling protects the cells from S phase mediated apoptosis. In addition, fibroblasts constitutively expressing a mutant E2F1 transcription factor (E2F1d87) have a lengthened S phase, due to a truncation of the cyclin A/cdk2 binding domain. Culture of these mutant-expressing cells on fibronectin did not shorten their S phase duration in spite of the fact that cyclin A levels and active cyclin A/cdk2 complex were significantly elevated. Thus, although the fibronectin signaling mechanisms culminating in elevated cyclin A were intact in these mutant E2F1 expressing cells, they were insensitive to the effects of this elevated cyclin A. The effect of the mutant E2F1d87 on slowing transit through S phase appears dominant over the effect of elevated cyclin A.

Original languageEnglish
Pages (from-to)549-555
Number of pages7
JournalInternational Journal of Oncology
Volume13
Issue number3
DOIs
StatePublished - Sep 1998
Externally publishedYes

Keywords

  • Cyclin A
  • Fibronectin matrix
  • S phase

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