Smad4的靶向缺失表明其在结肠癌细胞中对于转化生长因子β和激活素信号传导是必需的。
Targeted deletion of Smad4 shows it is required for transforming growth factor beta and activin signaling in colorectal cancer cells.
作者信息
Zhou S, Buckhaults P, Zawel L, Bunz F, Riggins G, Dai J L, Kern S E, Kinzler K W, Vogelstein B
机构信息
The Howard Hughes Medical Institute at Johns Hopkins University, Baltimore, MD 21231, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2412-6. doi: 10.1073/pnas.95.5.2412.
Abstract
Smad4 (DPC4) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) beta and related ligands. To directly test this hypothesis, the Smad4 gene was deleted through homologous recombination in human colorectal cancer cells. This deletion abrogated signaling from TGF-beta, as well as from the TGF-beta family member activin. These results provide unequivocal evidence that mutational inactivation of Smad4 causes TGF-beta unresponsiveness and provide a basis for understanding the physiologic role of this gene in tumorigenesis.
摘要
Smad4（DPC4）是一种候选肿瘤抑制基因，据推测它对于传递来自转化生长因子（TGF）β及相关配体的信号至关重要。为了直接验证这一假说，通过同源重组在人结肠癌细胞中删除了Smad4基因。这种缺失消除了来自TGF-β以及TGF-β家族成员激活素的信号传导。这些结果提供了明确的证据，表明Smad4的突变失活导致对TGF-β无反应，并为理解该基因在肿瘤发生中的生理作用提供了基础。
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