Transformed rat tracheal epithelial cells exhibit alterations in transforming growth factor‐β secretion and responsiveness

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Abstract
The purpose of our studies was to define abnormalities in the transforming growth factor-β (TGF-β) system of transformed rat tracheal epithelial (RTE) cells that might cause their abnormal growth behavior. We found that many, but not all, of the transformed cell lines were hyporesponsive or unresponsive to the growth inhibitory effects of TGF-β1. Scatchard and receptor cross-linking analyses indicated that loss of TGF-β1 responsiveness of transformed cells was probably not due to changes in receptor number or affinity, or to changes in expression of the three TGF-β-binding protein subtypes. Transformed cells were found to secrete far less TGF-β-like activity (<1/10) than primary cells. Cultured normal and transformed RTE cells expressed three TGF-β1 transcripts of 2.5, 1.9, and 1.4 kb. In contrast, rat kidney tissue, a rat embryo fibroblast cell line, and a rat liver cell line expressed only the typical 2.5-kb mRNA transcript commonly reported in the literature. In spite of the marked differences in TGF-α secretion between normal and transformed cells, their levels of TGF-β1 mRNA expression were similar. This suggests a change in the posttranscriptional regulation of TGF-β1 expression. TGF-β2 message was not detected in either normal or transformed RTE cells in culture. These findings are consistent with the hypothesis that the abnormal growth behavior of transformed RTE cells is at least in part due to disturbances of the TGF-β system.