Linked Life Data

17383120

Source:http://linkedlifedata.com/resource/pubmed/id/17383120

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-4-4
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30-41
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
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.
pubmed:affiliation
National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nan Wei Road, Beijing 100050, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural