Genome Research Center for Gastroenterology, Ajou University, School of Medicine, South Korea.
Cancer. 2010 Jun 1;116(11):2581-9. doi: 10.1002/cncr.25003.
We previously found the down-expression of SM22 in an experimental animal model of colorectal cancer by performing a proteomic analysis. In this study, we addressed the expression and molecular mechanisms of SM22 in human colorectal cancer.
To evaluate the expression of SM22 in colon cancers, Western blot and immunohistochemistry were performed in 13 normal, 14 adenomas, and 44 adenocarcinomas. To address the role of SM22 in colon carcinogenesis, SM22 was restored in the colon cancer cells by the transfection with the pIRES2 vector containing full-length SM22 cDNA and tested for tumorigenicity in vivo and in vitro.
SM22 was found to be significantly down-regulated in adenocarcinoma (58%) compared with adenoma (21.4%) and normal (15.3%). The loss of SM22 correlated with poor differentiation of tumor (P = 0.009) and lymph node metastasis (P = 0.029). Restoration of SM22 expression inhibited cell migration, colony-forming ability of cancer cells, and induced retardation of in vivo tumor growth in a xenograft model.
Loss of SM22 is a molecular signature of colon cancer and is closely associated with progression, differentiation, and metastasis of colon cancer. The restoration of SM22 leads to an inhibition of colon carcinogenesis in vivo and in vitro, suggesting that SM22 might potentially function as a novel tumor suppressor.
我们之前通过蛋白质组分析在结直肠癌的实验动物模型中发现 SM22 的表达下调。在这项研究中，我们研究了 SM22 在人结直肠癌中的表达和分子机制。
为了评估 SM22 在结肠癌中的表达，我们对 13 例正常组织、14 例腺瘤和 44 例腺癌进行了 Western blot 和免疫组织化学检测。为了研究 SM22 在结肠癌发生中的作用，我们通过转染含有全长 SM22 cDNA 的 pIRES2 载体使结肠癌细胞中 SM22 得到恢复，并在体内和体外检测其致瘤性。
与腺瘤（21.4%）和正常组织（15.3%）相比，腺癌（58%）中 SM22 的表达显著下调。SM22 的缺失与肿瘤分化不良（P=0.009）和淋巴结转移（P=0.029）相关。恢复 SM22 的表达抑制了癌细胞的迁移、集落形成能力，并在异种移植模型中诱导体内肿瘤生长的延迟。
SM22 的缺失是结肠癌的分子特征，与结肠癌的进展、分化和转移密切相关。SM22 的恢复导致体内和体外结肠癌发生的抑制，表明 SM22 可能作为一种新的肿瘤抑制因子发挥作用。
