Thompson J, Zimmermann W, Nollau P, Neumaier M, Weber-Arden J, Schrewe H, Craig I, Willcocks T
Institute of Immunobiology, University of Freiburg, Federal Republic of Germany.
J Biol Chem. 1994 Dec 30;269(52):32924-31.
We have determined the precise chromosomal location, the exon structure, and the expression pattern of CGM2, a member of the carcinoembryonic antigen (CEA) gene family. CGM2 cDNA was amplified by reverse transcription-polymerase chain reaction (RT/PCR) from the colon adenocarcinoma cell line, LS174T. A defective exon is missing from this cDNA clone, leading to a novel domain organization for the human CEA family with two immunoglobulin-like domains. The derived C-terminal domain predicts that the CGM2 protein is membrane-bound through a glycosyl phosphatidylinositol anchor. RT/PCR analyses identified CGM2 transcripts in mucinous ovarian and colonic adenocarcinomas as well as in adjacent colonic tissue, but not in other tumors including leukocytes from six chronic myeloid leukemia patients. Thus, unlike several other family members, CGM2 is not expressed in granulocytes but reveals a more CEA-like expression pattern. Northern blot analyses identified a 2.5-kilobase CGM2 mRNA that is strongly down-regulated in colonic adenocarcinomas compared with adjacent colonic mucosa, suggesting a possible tumor suppressor function. In addition, a 3.2-kilobase transcript was observed in a number of colon tumors that is not detectable in normal colonic tissue. This mRNA species could represent a tumor-specific CGM2 splice variant.
我们已经确定了癌胚抗原（CEA）基因家族成员CGM2的精确染色体定位、外显子结构和表达模式。通过逆转录-聚合酶链反应（RT/PCR）从结肠腺癌细胞系LS174T中扩增出CGM2 cDNA。该cDNA克隆缺失一个有缺陷的外显子，导致人CEA家族具有一种新的结构域组织，含有两个免疫球蛋白样结构域。推导的C末端结构域预测CGM2蛋白通过糖基磷脂酰肌醇锚定与膜结合。RT/PCR分析在黏液性卵巢癌和结肠腺癌以及相邻结肠组织中鉴定出CGM2转录本，但在包括6例慢性髓性白血病患者白细胞在内的其他肿瘤中未检测到。因此，与其他几个家族成员不同，CGM2不在粒细胞中表达，而是呈现出更类似CEA的表达模式。Northern印迹分析鉴定出一个2.5千碱基的CGM2 mRNA，与相邻结肠黏膜相比，其在结肠腺癌中强烈下调，提示可能具有肿瘤抑制功能。此外，在一些结肠肿瘤中观察到一个3.2千碱基的转录本，在正常结肠组织中无法检测到。这种mRNA可能代表一种肿瘤特异性的CGM2剪接变体。
