John R, El-Rouby N M, Tomasetto C, Rio M-C, Karam S M
Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, Al-Ain, UAE.
Histol Histopathol. 2007 Jul;22(7):743-51. doi: 10.14670/HH-22.743.
The pathogenesis of colon cancer is not well understood. This common type of cancer is generally believed to occur in a multistep process which involves alterations of various tumor suppressor genes and oncogenes during the progression through benign lesions towards carcinoma. TFF3 is a product of the colonic epithelium and has been implicated in colonic mucosal protection and also in the aggressiveness of colon cancer cells. The aim of this study was to analyze the expression of TFF3 during propagation towards cancer development in the human colon. Colonic tissues representing colitis, adenomatous polyposis, tubulovillous adenoma, and mucoid/adeno-carcinomas were processed for immunohistochemistry using an antibody specific for human TFF3. The results were correlated with those of PCNA-labeling, quantified, and compared with those of control tissues obtained from the safe margin of macroscopically normal colonic mucosa of patients with colon cancer. The data showed marked down-regulation of TFF3 expression in adenomatous polyposis, then TFF3 expression returns to about control level during adenoma and remains high during mucoid- and adeno-carcinomas. Colonic tissues with highly invasive cancer cells were characterized by statistically significant down-regulation of TFF3 expression. The changes observed in expression of TFF3 showed an inverse correlation with cell proliferation and suggest that it might play a protective role against colon carcinogenesis.
结肠癌的发病机制尚未完全明确。这种常见的癌症通常被认为是一个多步骤过程，在从良性病变发展为癌的进程中涉及多种肿瘤抑制基因和癌基因的改变。三叶因子3（TFF3）是结肠上皮的产物，与结肠黏膜保护以及结肠癌细胞的侵袭性有关。本研究的目的是分析TFF3在人类结肠向癌症发展过程中的表达情况。使用针对人类TFF3的特异性抗体对代表结肠炎、腺瘤性息肉病、管状绒毛状腺瘤和黏液腺癌/腺癌的结肠组织进行免疫组织化学处理。将结果与增殖细胞核抗原（PCNA）标记的结果相关联、进行量化，并与从结肠癌患者宏观正常结肠黏膜安全边缘获取的对照组织的结果进行比较。数据显示，在腺瘤性息肉病中TFF3表达明显下调，然后在腺瘤期间TFF3表达恢复到大约对照水平，在黏液腺癌和腺癌期间保持高水平。具有高侵袭性癌细胞的结肠组织的特征是TFF3表达在统计学上显著下调。TFF3表达的变化与细胞增殖呈负相关，提示其可能在预防结肠癌发生中发挥保护作用。
