Thompson J, Seitz M, Chastre E, Ditter M, Aldrian C, Gespach C, Zimmermann W
Institute of Immunobiology, University of Freiburg, Germany.
Cancer Res. 1997 May 1;57(9):1776-84.
Carcinoembryonic antigen gene family member 2 (CGM2), a member of the carcinoembryonic antigen (CEA) family, is expressed in normal colon and rectum but is down-regulated in colorectal adenocarcinomas. In situ hybridization studies demonstrate that CGM2 expression is limited to epithelial cells in the upper third of the crypts. Two other CEA family members, biliary glycoprotein (BGP) and nonspecific cross-reacting antigen (NCA), are similarly expressed, whereas CEA transcripts were found down to the base of the crypts but were less predominant in the upper region. Only low CGM2 and BGP mRNA levels were seen in colorectal tumors. CEA mRNA was expressed at an equivalent level in normal epithelia and in tumor cells, whereas NCA transcript levels were upregulated in tumor cells. Monoclonal antibodies that recognize the CGM2 protein reveal its presence on the apical membranes of epithelial cells in the upper third of the crypts but its absence from colorectal tumors, which do express the CEA and NCA-50/90 proteins. The newly cloned CGM2 3'-untranslated region was used to probe RNAs from adenomas, colorectal tumors at different stages of progression, and liver metastases of colorectal adenocarcinomas. This showed that CGM2 is already down-regulated in adenomas when compared to normal mucosae. The CGM2 expression pattern along with its sequence homology to BGP suggests a similar tumor suppressor function for CGM2.
癌胚抗原基因家族成员2（CGM2）是癌胚抗原（CEA）家族的一员，在正常结肠和直肠中表达，但在结肠直肠癌中表达下调。原位杂交研究表明，CGM2表达仅限于隐窝上三分之一的上皮细胞。另外两个CEA家族成员，胆汁糖蛋白（BGP）和非特异性交叉反应抗原（NCA）也有类似的表达，而CEA转录本在隐窝底部均可发现，但在上部区域不那么显著。在结肠直肠肿瘤中仅观察到低水平的CGM2和BGP mRNA。CEA mRNA在正常上皮细胞和肿瘤细胞中的表达水平相当，而NCA转录本水平在肿瘤细胞中上调。识别CGM2蛋白的单克隆抗体显示其存在于隐窝上三分之一上皮细胞的顶端膜上，但在表达CEA和NCA-50/90蛋白的结肠直肠肿瘤中不存在。新克隆的CGM2 3'-非翻译区用于探测腺瘤、不同进展阶段的结肠直肠肿瘤以及结肠直肠腺癌肝转移灶的RNA。这表明与正常黏膜相比，CGM2在腺瘤中就已经下调。CGM2的表达模式及其与BGP的序列同源性表明CGM2具有类似的肿瘤抑制功能。
