Down regulation of TGF-beta receptors in Human colorectal Canter

许多结肠直肠癌细胞对转化生长因子-β（TGF-β）的抗增殖作用具有抗性。TGF-β还作为癌细胞的旁分泌因子作用于其间充质细胞。本研究的目的是检测人结直肠癌组织中TGF-β及其受体的表达，并确定与癌症生长的任何关系。应用原位杂交和免疫组化方法检测10例大肠腺瘤、21例进展期大肠癌和10例正常大肠粘膜组织中TGF-β 1 Ⅰ型和Ⅱ型受体mRNA的表达。TGF-β受体mRNA主要在正常大肠上皮细胞和腺瘤中表达。然而，TGF-β受体的mRNA在21种人类晚期癌症中的7种中仅微弱表达。TGF-β_1 mRNA和蛋白在大肠癌组织中均呈强阳性表达。TGF-β 1蛋白和TGF-β 1受体mRNA在间质成纤维细胞和内皮细胞中也有分布。人结肠癌通过TGF-β受体的转录下调以及TGF-β对基质形成和血管生成的作用而逃避TGF-β介导的生长抑制，这表明TGF-β在完整宿主中结肠癌进展中的可能作用。

Many colorectal canoer cells are resistant to the anti-proliferative effects of transforming growth factor-beta (TGF-beta). TGF-beta also acts as paracrine factor from cancer cells on their mesenchymal cells. The aim of this study was to examine the expression of TGF-beta and its receptors in human colorectal cancer tissue and determined any relationship with cancer growth. In situ hybridization detection of TGF-beta_1 type I and type II receptor mRNA and immunohistochemical staining of TGF-beta_1 were performed using 10 human colorectal adenomas, 21 colorectal advanced cancers and 10 normal colorectal mucosas as control. TGF-beta receptor mRNAs were expressed mainly by normal colorectal epithelial cells and adenoma. However, mRNAs for TGF-beta receptors were only faintly, if at all, expressed in 7 of 21 human advanced cancers. In addition, intense signals of TGF-beta_1 mRNA and the protein were detected in all colorectal cancers. TGF-beta receptor mRNAs and TGF-beta_1 protein were also distributed in fibroblasts and endothelial cells in the interstitum. The escape of human colon cancer from TGF-beta-mediated growth inhibition by transcriptional down-regulation of TGF-beta receptors as well as the effects of TGF-beta on stroma formation and angiogenesis indicate a possible role for TGF-beta in the progression of colon cancer in an intact host.