Zhu Y, Richardson J A, Parada L F, Graff J M
Center for Developmental Biology, UT Southwestern Medical Center, Dallas, Texas 75235-9133, USA.
Cell. 1998 Sep 18;94(6):703-14. doi: 10.1016/s0092-8674(00)81730-4.
TGFbeta-related growth factors have been implicated in a variety of developmental and physiological processes in organisms ranging from nematodes to mammals. TGFbeta transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene. Smad3 mutant mice are viable and fertile. Between 4 and 6 months of age, the Smad3 mutant mice become moribund with colorectal adenocarcinomas. The neoplasms penetrate through the intestinal wall and metastasize to lymph nodes. These results directly implicate TGFbeta signaling in the pathogenesis of colorectal cancer and provide a compelling animal model for the study of human colorectal cancer.
转化生长因子β（TGFβ）相关生长因子参与了从线虫到哺乳动物等多种生物体的各种发育和生理过程。TGFβ通过Smad2、Smad3和Smad4将其信号转导至细胞内部。我们报道了小鼠Smad3基因的克隆及靶向敲除。Smad3突变小鼠可存活且能生育。在4至6月龄时，Smad3突变小鼠因结直肠癌而濒死。肿瘤穿透肠壁并转移至淋巴结。这些结果直接表明TGFβ信号传导参与结直肠癌的发病机制，并为研究人类结直肠癌提供了一个有说服力的动物模型。
