Silica induces cell cycle changes through PI-3K/AP-1 pathway in human embryo lung fibroblast cells

Xiaowei Jia, Bingci Liu, Meng Ye, Haifeng Liu, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Exposure to silica is associated with progressive pulmonary inflammation and fibrosis. Our previous study had demonstrated silica exposure could cause cell cycle alternation and activator protein-1 (AP-1) activation. This study showed that silica exposure induced phosphorylation of p70S6 kinase (p70S6K) and Akt in human embryo lung fibroblasts (HELFs). These changes were blocked by overexpression of dominant-negative mutants of phosphatidylinositol-3 kinase (Δp85) or Akt (DN-Akt), respectively. Moreover, pretreatment of cells with rapamycin, a specific p70S6K inhibitor, could inhibit silica-induced cell cycle alteration, AP-1 activation, and phosphorylation of p70S6K, but had no effect on Akt phosphorylation. This suggested that phosphatidylinositol-3 kinase (PI-3K)/AP-1 pathway was likely responsible for cell cycle changes. Furthermore, we observed the effect of the pathway on cell cycle regulatory proteins. Our results indicated that inactivation of PI-3K, Akt, or p70S6K could inhibit silica-induced overexpression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) and decreased expression of E2F-4. Taken together, silica could induce cell cycle changes through PI-3K/ AP-1 pathway in HELFs.

Original languageEnglish
Pages (from-to)613-619
Number of pages7
JournalCell Biochemistry and Function
Issue number7
StatePublished - Oct 2010


  • Cell cycle
  • PI-3K
  • Signaling pathways
  • Silica

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology


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