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Transforming growth factor beta expression and transformation of rat lung epithelial cells by crystalline silica (quartz)
Author(s) -
Williams A. Olufemi,
Knapton Alan D.,
Ifon Ekwere T.,
Saffiotti Umberto
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960301)65:5<639::aid-ijc14>3.0.co;2-2
Subject(s) - transformation (genetics) , quartz , beta (programming language) , lung , transforming growth factor beta , microbiology and biotechnology , chemistry , growth factor , pathology , transforming growth factor , cancer research , biology , materials science , medicine , biochemistry , gene , composite material , receptor , computer science , programming language
Crystalline silica (quartz) induces silicosis and associated peripheral lung carcinomas in rats. The role and pattern of expression of transforming growth factor (TGF)‐β1/β2 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 μg/cm 2 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‐TIC) 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‐β1 and desmoplasia. For comparison, a tumorigenic cell line derived from FRLE cells transformed with a mutated K‐ ras plasmid (RT‐CI) and cells subcultured from a corresponding nude mouse tumor (RT‐TI) and designated RT‐TIC were used. Whereas TGF‐β1 and TGF‐β2 inhibited the growth of QTT‐TIC and FRLE cells in a dose‐dependent fashion. RT‐TIC cells, containing an activated ras gene, were relatively unaffected. TGF‐β1 and TGF‐β2 mRNAs were expressed at higher levels in QTT‐TIC cells than in FRLE and RT‐TIC cells, and there was an increase in TGF‐βtype II receptor (TGF‐βR) mRNA expression in QTT‐TIC and RT‐TIC 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‐β1 protein on immunohistochemistry. The disparity between TGF‐β1 mRNA and TGF‐β1 protein expression in QTT tumors may be due to post‐transcriptional regulation of TGF‐β1. © 1996 Wiley‐Liss, Inc.