Journal Article

Opposed arsenite-induced signaling pathways promote cell proliferation or apoptosis in cultured lung cells

Andy T. Y. Lau, Muyao Li, Ronglin Xie, Qing-Yu He and Jen-Fu Chiu

in Carcinogenesis

Volume 25, issue 1, pages 21-28
Published in print January 2004 | ISSN: 0143-3334
Published online January 2004 | e-ISSN: 1460-2180 | DOI:
Opposed arsenite-induced signaling pathways promote cell proliferation or apoptosis in cultured lung cells

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Arsenic is a well-known carcinogen that possibly promotes tumors and the development of various types of cancer in individuals chronically exposed to arsenic in their work or living environment. Many studies have demonstrated the activation of mitogen-activated protein kinase (MAPK) in several cell types by using lethal concentrations of arsenic in the range of 50–500 µM. Since the exposure of humans to arsenic is normally at a much lower level in the workplace or in daily life, it is more relevant to study the effects of arsenic at this lower exposure level. In the present study we aimed at redefining the role of signal transduction pathways in arsenic-induced malignant transformation as well as apoptosis using our established in vitro rat lung epithelial cell model system. Our results indicate a molecular mechanism by which MAPK pathways might differentially contribute to cell growth regulation and cell death in response to different dosages of arsenite. A low level (2 µM) of arsenite stimulated extracellular signal-regulated kinase (ERK) signaling pathway and enhanced cell proliferation, and this arsenite-induced ERK activity was blocked by MEK inhibitor, PD98059. In contrast, a high level (40 µM) of arsenite stimulated the c-Jun N-terminal kinase (JNK) signaling pathway and induced cell apoptosis, and this arsenite-induced JNK activity was blocked by JNK inhibitor II, SP600125. The implications of these findings are that a high concentration of arsenic exposure causes apoptosis, whereas a low concentration of arsenic exposure is carcinogenic and may result in aberrant cell accumulation.

Keywords: AP-1, activator protein-1; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; GADD45, growth arrest and DNA damage-inducible 45; JNK, c-Jun N-terminal kinase; LEC, lung epithelial cell; MAPK, mitogen-activated protein kinase; NBB, Naphthol blue black; NF-κB, nuclear factor-kappaB

Journal Article.  6385 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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