Regulation of the hepatocyte cell cycle by type I collagen matrix: Role of cyclin D1

Linda K. Hansen, Jeffrey H. Albrecht

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Rat hepatocytes adherent to a rigid film of type I collagen will spread and enter S phase, while those attached to collagen gel or a dried collagen substrate remain round and quiescent. The current studies were initiated to determine the mechanism by which these different substrates differentially influence cell cycle progression. Cyclin D1 mRNA and protein expression and associated kinase activity was low on dried collagen relative to collagen film. In contrast, cyclin E and cdk2 protein levels were similar on the two substrates. Although cyclin E and cdk2 were present, cells on dried collagen lacked cdk2 kinase activity. p27 protein levels did not differ between dried collagen and film, but more p27 was associated with cdk2 in cells on dried collagen than those on collagen film. Cyclin D1 expression on collagen film was inhibited by cytochalasin D and exoenzyme C3, suggesting a role for the GTP-binding protein, Rho, in regulating cyclin D1 expression. Cyclin D1 over-expression induced hepatocytes into S phase in the absence of cell shape change on dried collagen or collagen gel. These results demonstrate a novel, substrate-dependent mechanism for cyclin D1 expression in hepatocytes, and also demonstrate that cyclin D1 over-expression allows shape-independent S phase entry.

Original languageEnglish (US)
Pages (from-to)2971-2981
Number of pages11
JournalJournal of cell science
Volume112
Issue number17
StatePublished - 1999

Keywords

  • Cell cycle
  • Cyclin D1
  • Extracellular matrix
  • Hepatocyte
  • Type I collagen

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