Nollau P, Scheller H, Kona-Horstmann M, Rohde S, Hagenmüller F, Wagener C, Neumaier M
Abteilung für Klinische Chemie, Medizinische Klinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Cancer Res. 1997 Jun 15;57(12):2354-7.
Among the members of the carcinoembryonic antigen (CEA) family, CD66a (human C-CAM) and CGM2 (CEA gene family member 2) mRNAs are frequently down-regulated in colorectal cancer. In contrast, nonspecific cross-reactive antigen (NCA) mRNA is overexpressed in the majority of these carcinomas. In animal models, the rodent homologues of CD66a have been shown to act as tumor suppressors, suggesting an important role in carcinogenesis. Here we investigate the mRNAs of CD66a, CGM2, and NCA in 22 human colorectal adenomas and the respective normal mucosa specimens by Northern blots. The expression of both CD66a and CGM2 changed in a concomitant fashion. Using oligonucleotides specific for the N-terminal domains, two CD66a transcripts 3.9 and 1.5 kb in size were identified. These showed a greater than 50% down-regulation in 20 of 22 and 18 of 22 adenomas, respectively. Reduction of the CGM2 message was observed in 21 of 22 cases. Complete or near-complete losses of the CD66a 3.9-kb mRNA and the CGM2 message were found in 13 of 22 and 15 of 22 of the tumors, respectively. The medians of CD66a and CGM2 expressions were between 0.3 and 0.0, respectively. The tumor:normal ratio of NCA mRNA expression was increased up to 2.4-fold in 11 of 22 adenomas. Altogether, these results compare well to the changes reported previously for colorectal carcinomas. The high frequency and early appearance of dysregulation of members of the carcinoembryonic antigen family during colorectal tumorigenesis suggests that these changes may be important for the development of the malignant phenotype.
在癌胚抗原（CEA）家族成员中，CD66a（人C-CAM）和CGM2（CEA基因家族成员2）的mRNA在结直肠癌中常被下调。相比之下，非特异性交叉反应抗原（NCA）的mRNA在大多数此类癌症中过度表达。在动物模型中，CD66a的啮齿动物同源物已被证明可作为肿瘤抑制因子，提示其在致癌过程中起重要作用。在此，我们通过Northern印迹法研究了22例人类结肠腺瘤及相应正常黏膜标本中CD66a、CGM2和NCA的mRNA。CD66a和CGM2的表达以伴随方式发生变化。使用针对N端结构域的寡核苷酸，鉴定出两种大小分别为3.9 kb和1.5 kb的CD66a转录本。在22例腺瘤中的20例和18例中，它们分别下调超过50%。在22例中的21例观察到CGM2信息减少。在22例肿瘤中的13例和15例中，分别发现CD66a 3.9-kb mRNA和CGM2信息完全或近乎完全缺失。CD66a和CGM2表达的中位数分别在0.3和0.0之间。在22例腺瘤中的11例中，NCA mRNA表达的肿瘤与正常组织比值增加高达2.4倍。总体而言，这些结果与先前报道的结直肠癌变化情况相符。癌胚抗原家族成员在结直肠癌发生过程中失调的高频率和早期出现表明，这些变化可能对恶性表型的发展很重要。
