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Roles of the ERK, JNK/AP-1/cyclin D1-CDK4 pathway in silica-induced cell cycle changes in human embryo lung fibroblast cells.

Authors
Jia-X; Liu-B; Shi-X; Ye-M; Zhang-F; Liu-H
Source
Cell Biol Int 2011 Jul; 35(7):697-704
NIOSHTIC No.
20039628
Abstract
Silica is a potent occupational fibrogenic agent capable of inducing lung fibrosis and many other lung diseases. Our current study focused on the signalling pathways regulating cell cycle changes in HELF (human embryo lung fibroblast) after silica (alpha-quartz) exposure. Our results showed silica exposure could lead to cell cycle changes. The cell cycle alternations were accompanied with overexpression of cyclin D1 and CDK4 (cyclin-dependent kinase 4) in a time-dependent manner. Silica exposure also decreased E2F-4 expression in HELF. These changes were blocked by overexpression of dominant-negative mutants of ERK (extracellular signal-regulated protein kinase) or the JNK (stress-activated c-Jun NH(2)-terminal kinase), respectively. Moreover, pretreatment of cells with curcumin, an activation of AP-1 (activator protein-1) inhibitor, inhibited silica-induced cell cycle alteration, the decreased expression of E2F-4 and overexpression of cyclin D1 and CDK4. Furthermore, both antisense cyclin D1 and antisense CDK4 can block silica-induced cell cycle changes. These results suggest that silica exposure can induce cell cycle changes, which may be mediated through ERK, JNK/AP-1/cyclin D1-CDK4-dependent pathway.
Keywords
Biohazards; Biological-effects; Biological-systems; Cancer-rates; Cell-function; Cell-metabolism; Cell-transformation; Cellular-function; Cellular-reactions; Fibrogenicity; Fibrous-bodies; Particulate-dust; Particulates; Work-areas; Worker-health; Work-operations; Author Keywords: cell cycle; HELF; lung fibrosis; occupational; signalling pathway; silica
CODEN
CBIIEV
CAS No.
7631-86-9
Publication Date
20110701
Document Type
Journal Article
Email Address
bcliu@263.net
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
B09282011
Issue of Publication
7
ISSN
1065-6995
NIOSH Division
HELD
Source Name
Cell Biology International
State
WV
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