title: Transforming growth factor beta expression and transformation of rat lung epithelial cells by crystalline silica (quartz).
abstract: Crystalline silica (quartz) induces silicosis and associated peripheral lung carcinomas in rats. The role and pattern of expression of transforming growth factor (TGF)-beta1/beta2 mRNA transcripts were investigated in the fetal rat lung epithelial cell line FRLE, its neoplastic transformants and derived tumors in athymic nude mice. FRLE cells, treated with 100 microgram/cm2 of quartz in serum-free medium, gave rise to phenotypically altered, tumorigenic cells. Quartz-treated, transformed and tumorigenic cells, subcultured directly (QTT-C1) or after growth in soft agar (QTT-C2), formed tumors in athymic nude mice (QTT-T1). Cells subcultured from the tumors (QTT-T1C) were also tumorigenic in nude mice (QTT-T2). QTT-T1 and QTT-T2 tumors were poorly differentiated carcinomas with variable amounts of extracellular matrix-associated TGF-beta1 and desmoplasia. For comparison, a tumorigenic cell line derived from FRLE cells transformed with a mutated K-ras plasmid (RT-C1) and cells subcultured from a corresponding nude mouse tumor (RT-T1) and designated RT-T1C were used. Whereas TGF-beta1 and TGF-beta2 inhibited the growth of QTT-T1C and FRLE cells in a dose-dependent fashion, RT-T1C cells, containing an activated ras gene, were relatively unaffected. TGF-beta1 and TGF-beta2 mRNAs were expressed at higher levels in QTT-T1C cells than in FRLE and TR-T1C cells, and there was an increase in TGF-beta type II receptor (TGR-betaR) mRNA expression in QTT-T1C and RT-T1C cells compared to FRLE cells. Carcinomas in nude mice derived from QTT and RT cells and silicosis-associated lung carcinomas induced in rats by intra-tracheal quartz did not express either active or latent forms of TGF-beta1 protein on immunohistochemistry. The disparity between TGF-beta1 mRNA and TGF-beta1 protein expression in QTT tumors may be due to post-transcriptional regulation of TGF-beta1.
authors.affiliation: Laboratory of Experimental Pathology, Division of Cancer Etiology, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: A O
authors.initials: AO
authors.lastname: Williams
authors.forename: A D
authors.initials: AD
authors.lastname: Knapton
authors.forename: E T
authors.initials: ET
authors.lastname: Ifon
authors.forename: U
authors.initials: U
authors.lastname: Saffiotti
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009374:Neoplasms, Experimental / Q000473:pathology; D011510:Proteolipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012822:Silicon Dioxide; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D012822:Silicon Dioxide