CHARACTERIZATION OF A 3RD TRANSFORMING GROWTH-FACTOR BETA(1) TRANSCRIPT IN RAT TRACHEAL EPITHELIAL-CELLS

It has been previously reported (R. W. Steigerwalt et al., Mol. Carcin og., 5: 32-40, 1992) that primary cultures of rat tracheal epithelial (RTE) cells and immortalized RTE cell lines produce three mRNA transcr ipts [2.5, 1.9, 1.4 kilobases (kb)] which hybridize to a murine transf orming growth factor beta1 (TGF-beta1) complementary DNA probe. In thi s report, we show that the 1.9- and 1.4-kb transcripts are not detecta ble by Northern analysis of resting adult trachea but are induced in r egenerating tracheal grafts and tumors formed from transformed RTE cel ls. Northern analysis of the TGF-beta1 transcripts with subclones of t he murine complementary DNA demonstrate that the 1.4-kb transcript lac ks much of the 5' untranslated region (UTR). RNase protection analysis was used to map the transcriptional start site of the 1.4-kb transcri pt to within 30-40 base pairs of the first ATG codon. No differences i n the coding or 3' UTR were detected between the 1.4-kb and the 2.5-kb transcripts. Although RTE cells produce a 1.9-kb TGF-beta1 mRNA, we w ere unable to detect a previously reported unique 3' UTR, which we fou nd to be almost identical to a rat mitochondrial ATPase sequence. Beca use the 1.4-kb transcript is missing most of the long GC-rich 5' UTR, it may be translated at a different rate than the 2.5- and 1.9-kb tran scripts, or it may code for an intracellular form of TGF-beta1. The 1. 4-kb transcript has been observed under several conditions of injury o r stress and, therefore, may be an important component of the TGF-beta 1 response to these conditions.