mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats.
Human malignant mesotheliomas are induced almost exclusively by fibrous dusts. The nature of interactions between fibers and target cells, and the molecular mechanisms leading to tumorigenesis, are not yet understood. Here, the mRNA expression patterns at different stages of asbestos-induced carcinogenesis in rats were monitored by suppression subtractive hybridization (SSH) and array assay. Several genes were upregulated in pretumorous tissues from asbestos-treated rats, in asbestos-induced tumors and in cells treated with asbestos in vitro. The upregulation of the proto-oncogene c-myc, fra-1 and egfr in fiber-induced carcinogenesis was demonstrated at different stages of carcinogenesis. A possible role of Fra-1 as one of the dimeric proteins generating the AP-1 transcription factor was substantiated by its dose-dependent expression in mesothelial cells treated with asbestos in vitro. The upregulation of osteopontin (an extracellular matrix protein) and of zyxin and integrin-linked kinase (intracellular proteins associated with the focal adhesion contact), indicate that fibers may affect integrin-linked signal transduction and extracellular matrix proteins.
Sandhu
H
H
Department of Experimental Toxicology, Medical Institute of Environmental Hygiene at the Heinrich Heine University, Auf'm Hennekamp 50,40225 Düsseldorf, Germany.
Dehnen
W
W
Roller
M
M
Abel
J
J
Unfried
K
K
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics; D016259:Genes, myc; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000099169:Fos-Related Antigen 1
D017638:Asbestos, Crocidolite; D002273:Carcinogens; D017931:DNA Primers; D066246:ErbB Receptors; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000099169:Fos-Related Antigen 1; C000715470:MAS1 protein, human