Alteration of cell growth and morphology by overexpression of transforming growth factor β type II receptor in human lung adenocarcinoma cells
Alteration of cell growth and morphology by overexpression of transforming growth factor β type II receptor in human lung adenocarcinoma cells
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DOI：
10.1016/s0169-5002(00)00169-0
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发表时间：
2001-02-01
期刊：
影响因子：
5.3
通讯作者：
Kim, YW
中科院分区：
文献类型：
--
作者：
Kim, TK;Mo, EK;Kim, YW
TGF-β是细胞生长的有效抑制性调节剂。其通过形成异聚激酶复合物的I型（RI）和II型（RII）受体之间的相互作用转导。这些受体的异常表达已在几种人类上皮癌中被鉴定，并已被证明与对TGF-β的抗性高度相关。本研究我们研究了RI和RII在13个人非小细胞肺癌细胞系（NSCLC）中的表达，并证明了在5个肺癌细胞系中RII表达降低或丧失，但RI没有。在这些细胞系中，RII在NCI-H358腺癌中的作用。其缺乏RII并且对TGF-β不敏感。通过用表达全长TGF-β RI 1的重组逆转录病毒转导该细胞系来研究。稳定转染的细胞显示RII mRNA和蛋白表达显著增加。这些细胞对外源性TGF-β 1的反应是以剂量依赖的方式抑制增殖，并伴随着与对照细胞不同的形态学变化而发生G1期阻滞。我们还研究了显性负性RII（dnRII）在NCI-H441腺癌中是否过表达。其敏感但表达低水平的RII。可以阻断通过受体复合物的信号传导。通过表达逆转录病毒dnRII构建体来过度表达这种激酶结构域截短的RII，导致对TGF-β 1反应的能力丧失，并表现出不受控制的生长。这些结果表明野生型TGF-β RII表达的缺失与人肾癌细胞的癌变密切相关。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
TGF-beta is a potent inhibitory regulator of cell growth. which is transduced through interaction between type I (RI) and type II (RII) receptors that form heteromeric kinase complexes. Abnormal expression of these receptors has been identified in several human epithelial cancers and has been shown to be highly associated with resistance to TGF-beta (.) In this study. we investigated the expression of RI and RII in 13 human non-small cell lung cancer cell lines (NSCLCs) and demonstrated decreased or loss of RII expression in five lung cancer cell lines, but not of RI. Of these cell lines, the role of RII in NCI-H358 adenocarcinoma. which lacks RII and is insensitive to TGF-beta. was investigated by transducing this cell line with a recombinant retrovirus expressing full-length TGF-beta RI1. Stably transfected cells showed significant increase in RII mRNA and protein expression. These cells responded to exogenous TGF-beta1 with suppressed proliferation in a dose-dependent manner and G1 arrest accompanied by morphological change distinct from control cells. We also investigated whether overexpression of dominant-negative RII (dnRII) in NCI-H441 adenocarcinoma. which is sensitive but expresses low levels of RII. could block signaling through the receptor complex. The overexpression of this kinase-domain-truncated RII by expressing the retroviral dnRII construct led to loss of the ability to respond to TGF-beta1 and an exhibition of uncontrolled growth. These results suggest a close association between the loss of the expression of wild-type TGF-beta RII and carcinogenesis in human lune cancer cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.