当前位置： SCI文献检索 > TOXICOLOGY LETTERS期刊下所有文献 > Phosphatidylinositol-3 kinase/Akt/p70S6K/AP-1 signaling pathway mediated benzo(a)pyrene-induced cell cycle alternation via cell cycle regulatory proteins in human embryo lung fibroblasts.

Phosphatidylinositol-3 kinase/Akt/p70S6K/AP-1 signaling pathway mediated benzo(a)pyrene-induced cell cycle alternation via cell cycle regulatory proteins in human embryo lung fibroblasts.

Abstract：

:Benzo(a)pyrene (B(a)P), a potent environmental procarcinogen, has been shown to cause cell cycle alternation. However, the mechanisms involved in this effect are not well understood yet. Our current results demonstrated that B(a)P exposure led to cell proliferation and a 33.5% increase in S phase cells as well as a 26.8% decrease in G1 phase cells in human embryo lung fibroblasts (HELFs). Those cell cycle alternations were accompanied with transactivation of activator protein-1 (AP-1) and phosphorylation of Akt and p70(S6K). These changes were blocked by overexpression of dominant negative mutants of phosphatidylinositol-3 kinase (Deltap85) or Akt (DN-Akt), respectively. Moreover, pretreatment of cells with rapamycin, a specific p70(S6K) inhibitor, inhibited B(a)P-induced AP-1 activation, cell cycle alteration and phosphorylation of p70(S6K), but had no effect on Akt phosphorylation. Our results, therefore, suggest that phosphatidylinositol-3 kinase (PI-3K)/Akt/p70(S6K)/AP-1 pathway participates in B(a)P-induced cell cycle alternations. Furthermore, we explored the effect of this pathway on cell cycle regulatory proteins. B(a)P markedly increases in the expression of cyclin D1 and E2F1 and phosphorylation of retinoblastoma protein (Rb). In addition, we found that inactivation of PI-3K, Akt or p70(S6K) could eliminate those effects on cell cycle regulatory proteins. Collectively, PI-3K/Akt/p70(S6K)/AP-1 pathway mediated B(a)P-induced alternation of cell cycle through regulation of cell cycle regulatory proteins such as cyclin D1, E2F1, and Rb in HELFs.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Gao A,Liu B,Shi X,Jia X,Ye M,Jiao S,You B,Huang C

doi

10.1016/j.toxlet.2007.02.008

subject

Has Abstract

pub_date

2007-04-05 00:00:00

pages

30-41

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(07)00069-0

journal_volume

170

pub_type

杂志文章

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