Steigerwalt R W, Rundhaug J E, Nettesheim P
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Mol Carcinog. 1992;5(1):32-40. doi: 10.1002/mc.2940050108.
The purpose of our studies was to define abnormalities in the transforming growth factor-beta (TGF-beta) 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-beta 1. Scatchard and receptor cross-linking analyses indicated that loss of TGF-beta 1 responsiveness of transformed cells was probably not due to changes in receptor number or affinity, or to changes in expression of the three TGF-beta-binding protein subtypes. Transformed cells were found to secrete far less TGF-beta-like activity (less than 1/10) than primary cells. Cultured normal and transformed RTE cells expressed three TGF-beta 1 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-beta secretion between normal and transformed cells, their levels of TGF-beta 1 mRNA expression were similar. This suggests a change in the posttranscriptional regulation of TGF-beta 1 expression. TGF-beta 2 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-beta system.
我们研究的目的是确定转化的大鼠气管上皮（RTE）细胞的转化生长因子-β（TGF-β）系统中的异常情况，这些异常可能导致其异常生长行为。我们发现，许多（但不是全部）转化细胞系对TGF-β1的生长抑制作用反应低下或无反应。Scatchard分析和受体交联分析表明，转化细胞对TGF-β1反应性的丧失可能不是由于受体数量或亲和力的变化，也不是由于三种TGF-β结合蛋白亚型表达的变化。我们发现，转化细胞分泌的TGF-β样活性远低于原代细胞（不到1/10）。培养的正常和转化RTE细胞表达三种大小分别为2.5、1.9和1.4 kb的TGF-β1转录本。相比之下，大鼠肾脏组织、大鼠胚胎成纤维细胞系和大鼠肝细胞系仅表达文献中通常报道的典型2.5 kb mRNA转录本。尽管正常细胞和转化细胞之间TGF-β分泌存在显著差异，但它们的TGF-β1 mRNA表达水平相似。这表明TGF-β1表达的转录后调控发生了变化。在培养的正常或转化RTE细胞中均未检测到TGF-β2信息。这些发现与以下假设一致，即转化RTE细胞的异常生长行为至少部分归因于TGF-β系统的紊乱。
