Prat M, Narsimhan R P, Crepaldi T, Nicotra M R, Natali P G, Comoglio P M
Dept. of Biomedical Sciences and Oncology, University of Turin Medical School, Italy.
Int J Cancer. 1991 Sep 30;49(3):323-8. doi: 10.1002/ijc.2910490302.
The human c-MET oncogene encodes a transmembrane tyrosine kinase (p190c-met) with structural and functional features of a growth-factor receptor. Monoclonal antibodies (MAbs) have been used to investigate the distribution of the c-Met protein in human normal and neoplastic tissues. By immunofluorescence microscopy homogeneous expression was detected in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Positive staining was also found in epithelial cells of the endometrium and ovary, and in basal keratinocytes of esophagus and skin. By Northern blot analysis, high levels of c-met messenger RNA were detected in specimens of liver, gastro-intestinal tract and kidney. c-met-specific mRNA was also found in thyroid, pancreas and placenta, in which organs c-Met protein was barely detectable by immunofluorescence. The antibodies revealed expression of c-MET protein in hepatomas (11/14), carcinomas of colon and rectum (19/21), stomach (11/22), kidney (16/19), ovary (9/17) and skin (7/17). Carcinomas of the lung (13/20), thyroid (11/13) and pancreas (5/7) were also positive. In these last cases (lung, thyroid and pancreas) tumor cells were homogeneously stained by the antibodies, whereas in their normal counterparts staining was barely detectable. These data suggest that the receptor encoded by c-MET plays a physiological role in epithelial cell growth and that its expression is altered in human carcinomas.
人类c-MET癌基因编码一种具有生长因子受体结构和功能特征的跨膜酪氨酸激酶(p190c-met)。单克隆抗体(MAbs)已被用于研究c-Met蛋白在人类正常组织和肿瘤组织中的分布。通过免疫荧光显微镜检查,在正常肝细胞以及胃、小肠和大肠的上皮细胞中检测到均匀表达。在子宫内膜和卵巢的上皮细胞以及食管和皮肤的基底角质形成细胞中也发现了阳性染色。通过Northern印迹分析,在肝脏、胃肠道和肾脏标本中检测到高水平的c-met信使RNA。在甲状腺、胰腺和胎盘中也发现了c-met特异性mRNA,而在这些器官中通过免疫荧光几乎检测不到c-Met蛋白。这些抗体揭示了c-MET蛋白在肝癌(11/14)、结肠癌和直肠癌(19/21)、胃癌(11/22)、肾癌(16/19)、卵巢癌(9/17)和皮肤癌(7/17)中的表达。肺癌(13/20)、甲状腺癌(11/13)和胰腺癌(5/7)也呈阳性。在这些最后提及的病例(肺癌、甲状腺癌和胰腺癌)中,肿瘤细胞被抗体均匀染色,而在其正常对应组织中几乎检测不到染色。这些数据表明,由c-MET编码的受体在上皮细胞生长中起生理作用,并且其表达在人类癌症中发生改变。