Transforming growth factor beta type I receptor kinase mutant associated with metastatic breast cancer.
Transforming growth factor beta type I receptor kinase mutant associated with metastatic breast cancer.
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发表时间：
1998-11
期刊：
影响因子：
11.2
通讯作者：
Taiping Chen;D. Carter;L. Garrigue-Antar;M. Reiss
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文献类型：
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作者：
Taiping Chen;D. Carter;L. Garrigue-Antar;M. Reiss
恶性乳腺癌细胞系对转化生长因子-β(转化生长因子-β)介导的细胞周期停滞常常是耐药的。为了确定转化生长因子-β受体耐药的分子机制，我们对乳腺癌及其腋窝淋巴结转移相关的转化生长因子-β受体I(TbetaR-I)和II(TbetaR-II)基因进行了全面的结构分析。未发现TbetaR-II基因表达缺失(n=14)或结构改变(n=30)的证据。然而，31例原发癌中有2例和12例淋巴结转移癌中有5例携带C到A颠换突变，导致TbetaR-I受体基因第387位密码子(S387Y)丝氨酸到酪氨酸替换。与野生型TbetaR-I相比，TbetaR-I突变体介导转化生长因子-β依赖的基因表达的能力减弱。S387Y是第一个在人类癌症中报道的TbetaR-I基因突变，在本系列中主要与淋巴转移有关。
Malignant breast carcinoma cell lines are frequently refractory to transforming growth factor beta (TGF-beta)-mediated cell cycle arrest. To identify molecular mechanisms of TGF-beta resistance, we have conducted a comprehensive structural analysis of the TGF-beta receptor types I (TbetaR-I) and II (TbetaR-II) genes in primary human breast carcinomas and associated axillary lymph node metastases. No evidence for loss of expression (n=14) or structural alterations of the TbetaR-II gene (n=30) were identified. However, 2 of 31 primary carcinomas and 5 of 12 lymph node metastases carried a C to A transversion mutation resulting in a serine to tyrosine substitution at codon 387 (S387Y) of the TbetaR-I receptor gene. This TbetaR-I mutant has a diminished ability to mediate TGF-beta-dependent effects on gene expression as compared with wild-type TbetaR-I. S387Y is the first reported mutation in the TbetaR-I gene in human cancer that was primarily associated with lymph node metastases in the present series.