GENETIC CHANGES IN THE TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) TYPE-II RECEPTOR GENE IN HUMAN GASTRIC-CANCER CELLS - CORRELATION WITH SENSITIVITY TO GROWTH-INHIBITION BY TGF-BETA
GENETIC CHANGES IN THE TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) TYPE-II RECEPTOR GENE IN HUMAN GASTRIC-CANCER CELLS - CORRELATION WITH SENSITIVITY TO GROWTH-INHIBITION BY TGF-BETA
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DOI：
10.1073/pnas.91.19.8772
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发表时间：
1994-09-13
影响因子：
11.1
通讯作者：
SPORN, MB
中科院分区：
文献类型：
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作者：
PARK, KC;KIM, SJ;SPORN, MB
我们已经发现，在对TGF-β的生长抑制作用有抗性的人胃癌细胞系中，TGF-β II型受体基因发生了几种遗传变化。Southern印迹分析显示，在8个细胞系中的2个中II型受体基因缺失，在另外2个细胞系中扩增。我们研究的对TGF-β生长抑制敏感的单细胞系显示II型受体基因没有结构异常。一些对TGF-β的生长抑制作用有抗性的胃癌细胞表达截短的或不可检测的TGF-β II型受体mRNA，而保留对TGF-β的生长抑制作用的应答性的胃癌细胞表达完整大小的II型受体mRNA。免疫沉淀，然后Western印迹分析显示TGF-β II型受体表达的平行变化。我们的研究结果表明，逃避自分泌或旁分泌生长控制的TGF-β在癌变过程中可能涉及TGF-β II型受体基因本身的遗传变化或其mRNA的表达改变的机制之一。
We have found several genetic changes in the TGF-beta type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-beta. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-beta showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-beta express either truncated or no detectable TGF-beta type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-beta expresses a full-size type II receptor mRNA. Immuno-precipitation followed by Western blot analysis showed parallel changes in TGF-beta type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve genetic changes in the TGF-beta type II receptor gene itself or altered expression of its mRNA.