This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Related articles in AJRCMB Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Heintz, N. H. Articles by Mossman, B. T. PubMed PubMed Citation Articles by Heintz, N. H. Articles by Mossman, B. T.

Asbestos, Lung Cancers, and Mesotheliomas

From Molecular Approaches to Targeting Tumor Survival Pathways

¹ Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont

Correspondence and requests for reprints should be addressed to Brooke T. Mossman, Ph.D., Department of Pathology, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405-0068. E-mail: brooke.mossman{at}uvm.edu

Abstract

Fifteen years have passed since we published findings in the AJRCMB demonstrating that induction of early response fos/jun proto-oncogenes in rodent tracheal and mesothelial cells correlates with fibrous geometry and pathogenicity of asbestos. Our study was the first to suggest that the aberrant induction of signaling responses by crocidolite asbestos and erionite, a fibrous zeolite mineral associated with the development of malignant mesotheliomas (MMs) in areas of Turkey, led to altered gene expression. New data questioned the widely held belief at that time that the carcinogenic effects of asbestos in the development of lung cancer and MM were due to genotoxic or mutagenic effects. Later studies by our group revealed that proto-oncogene expression and several of the signaling pathways activated by asbestos were redox dependent, explaining why antioxidants and antioxidant enzymes were elevated in lung and pleura after exposure to asbestos and how they alleviated many of the phenotypic and functional effects of asbestos in vitro or after inhalation. Since these original studies, our efforts have expanded to understand the interface between asbestos-induced redox-dependent signal transduction cascades, the relationship between these pathways and cell fate, and the role of asbestos and cell interactions in development of asbestos-associated diseases. Of considerable significance is the fact that the signal transduction pathways activated by asbestos are also important in survival and chemoresistance of MMs and lung cancers. An understanding of the pathogenic features of asbestos fibers and dysregulation of signaling pathways allows strategies for the prevention and therapy of asbestos-related diseases.

Key Words: proto-oncogenes • mitogen-activated protein kinases • epidermal growth factor receptor • activator protein-1 • nuclear factor-B

CLINICAL RELEVANCE This review will help guide individuals in research on fiber carcinogenesis. The article also outlines therapeutic approaches for treatment of asbestos-related diseases that have been developed in the recent past.

 

Related articles in AJRCMB:

Asbestos and Lung Disease

Arnold R. Brody
AJRCMB 2010 42: 131-132. [Full Text]  

This article has been cited by other articles:

				A. R. Brody Asbestos and Lung Disease Am. J. Respir. Cell Mol. Biol., February 1, 2010; 42(2): 131 - 132. [Full Text] [PDF]