INACTIVATION OF THE TYPE-II TGF-BETA RECEPTOR IN COLON-CANCER CELLS WITH MICROSATELLITE INSTABILITY
INACTIVATION OF THE TYPE-II TGF-BETA RECEPTOR IN COLON-CANCER CELLS WITH MICROSATELLITE INSTABILITY
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DOI：
10.1126/science.7761852
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发表时间：
1995-06-02
期刊：
影响因子：
56.9
通讯作者：
WILLSON, JKV
中科院分区：
文献类型：
--
作者：
MARKOWITZ, S;WANG, J;WILLSON, JKV
转化生长因子-β(TGF-β)是一种强有力的上皮细胞生长抑制因子。微卫星不稳定性高的人结肠癌细胞系被发现含有II型转化生长因子-β受体(RII)基因突变。由于三种不同的突变，确定了八个这样的例子。这些突变集中在RII基因的小重复序列中，伴随着细胞表面RII受体的缺失，通常与少量的RII转录本相关。RII突变通过诱导细胞逃避转化生长因子-β介导的生长控制，将DNA修复缺陷与肿瘤进展的特定途径联系起来。
Transforming growth factor-beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Human colon cancer cell lines with high rates of microsatellite instability were found to harbor mutations in the type II TGF-beta receptor (RII) gene. Eight such examples, due to three different mutations, were identified. The mutations were clustered within small repeated sequences in the RII gene, were accompanied by the absence of cell surface RII receptors, and were usually associated with small amounts of RII transcript. RII mutation, by inducing the escape of cells from TGF-beta-mediated growth control, links DNA repair defects with a specific pathway of tumor progression.