Fukushima T, Mashiko M, Takita K, Otake T, Endo Y, Sekikawa K, Takenoshita S
Dept. of Surgery 2, Fukushima Medical University School of Medicine, Fukushima City, Japan.
J Exp Clin Cancer Res. 2003 Jun;22(2):315-20.
Transforming growth factor-beta(TGF-beta) is known to play an important role in controlling embryonal development, cell proliferation and homeostasis. The purpose of this study is to elucidate the involvement of the TGF-beta pathway in colorectal carcinogenesis. DNA was extracted from 100 patients with colorectal cancer. Then, all coding regions of the TGF-beta type II receptor (TRII) and the genes for Smad2, Smad3, Smad4, Smad6, and Smad7 were analyzed by PCR-SSCP and direct sequencing. Also, a LOH analysis of 18q21, where the Smad2 and Smad4 genes are located, was performed. We detected 11 cases of frameshift mutation in the TRII gene (11%) and 5 cases of point mutations in the Smad4 gene (5.0%); LOH at 18q21 was detected with 33% frequency. No abnormalities were found in the genes for Smad2, Smad3, Smad6, and Smad7. These results suggest that the abnormalities of TRII and Smad4 play an important role inhibiting TGF-beta signaling in colorectal carcinogenesis.
已知转化生长因子-β（TGF-β）在控制胚胎发育、细胞增殖和体内平衡中发挥重要作用。本研究的目的是阐明TGF-β信号通路在结直肠癌发生中的作用。从100例结直肠癌患者中提取DNA。然后，通过PCR-SSCP和直接测序分析TGF-βⅡ型受体（TRII）以及Smad2、Smad3、Smad4、Smad6和Smad7基因的所有编码区。此外，对Smad2和Smad4基因所在的18q21进行杂合性缺失（LOH）分析。我们在TRII基因中检测到11例移码突变（11%），在Smad4基因中检测到5例点突变（5.0%）；18q21的LOH检测频率为33%。在Smad2、Smad3、Smad6和Smad7基因中未发现异常。这些结果表明，TRII和Smad4的异常在结直肠癌发生中抑制TGF-β信号传导方面发挥重要作用。
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