Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas.

Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas.
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DOI:
10.1111/j.1349-7006.1992.tb02356.x
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发表时间:
1992-01
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Tahara E
Tahara E
中科院分区:
其他
文献类型:
--
作者:
Ito M;Yasui W;Nakayama H;Yokozaki H;Ito H;Tahara E

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应用北方印迹杂交、免疫组化、亲和标记和凝胶阻滞分析等方法检测人胃癌组织中转化生长因子β(TGF-β)及其受体和TGF-β抑制元件(TIE)结合蛋白的表达。TGF-β mRNA在肿瘤和正常组织中均有不同程度的表达。免疫组织化学证实肿瘤细胞内存在TGF-β表达。在17例人胃癌组织中,与相应的正常粘膜相比,14例(82%)显示TGF-β的I型受体(65 kDa)水平降低。有趣的是,在14个肿瘤中的7个肿瘤组织中TIE结合蛋白的水平低于正常粘膜。人胃癌细胞系TMK-1,其生长受到TGF-β的抑制,仅具有TGF-β的I型受体,并显示出高水平的TIE结合蛋白。相反,MKN-1,一种TGF-β-抗性细胞系,表现出极低水平的TGF-β受体,并且没有TIE-结合蛋白。这些结果总体上表明,尽管人胃癌细胞产生TGF-β,但它们显示TGF-β I型受体减少和低水平的TIE结合蛋白,导致逃避TGF-β的生长抑制。
The expressions of transforming growth factor beta (TGF‐β) and its receptor and TGF‐β inhibitory element (TIE)‐binding protein were examined on human gastric carcinomas by Northern blot hybridization, immunohistochemistry, affinity labeling and gel retardation analysis. TGF‐β mRNA was expressed in tumor and normal tissues at various levels. Immunohistochemically, TGF‐β expression was confirmed to be present within tumor cells. Out of the 17 human gastric carcinoma tissues, 14 (82%) showed a reduction in the level of type I receptor (65 kDa) for TGF‐β when compared to corresponding normal mucosas. Interestingly, in seven of the 14 tumors the level of TIE‐binding protein in the tumor tissue was lower than that in normal mucosa. Human gastric carcinoma cell line TMK‐1, whose growth was inhibited by TGF‐β, had only type I receptor for TGF‐β and showed a high level of TIE‐binding protein. Conversely, MKN‐1, a TGF‐β ‐resistant cell line, exhibited an extremely low level of TGF‐β receptor and had no TIE‐binding protein. These results overall indicate that although human gastric carcinoma cells produced TGF‐β, they showed a reduction in TGF‐β type I receptor and a low level of TIE‐binding protein, resulting in escape from growth inhibition by TGF‐β.