Significance of c-erbB-2 and its ligand affecting malignant potential of urological carcinomas.

检测尿路上皮癌组织中c-erbB-2和人NDF基因的表达。Southern杂交结果显示，32例尿路上皮癌中有2例(6.3%)有c-erbB-2基因扩增，但未见人NDF基因的扩增或重排。采用单链构象多态分析(SSCP)方法检测p53基因外显子4至外显子9的突变情况，以探讨p53基因突变是否影响c-erbB-2基因扩增的发生。SSCP检测到9例(28.1%)p53基因点突变，仅1例肿瘤同时存在c-erbB-2基因扩增，提示c-erbB-2基因扩增不需要p53基因突变。在32例尿路上皮癌中有10例(31.0%)C-erbB-2基因过度表达，而人NDF基因在正常膀胱组织、膀胱肿瘤和人膀胱癌细胞LIN(5637)中低水平表达。这些结果提示尿路上皮癌的发生和发展是由人NDF和c-erbB-2基因介导的自分泌机制促进的。已有研究表明，受体类型的细胞膜蛋白HER4是激活c-erbB-2蛋白所必需的。对20例肾癌组织中NDF、c-erbB-2和HER4基因的表达进行了研究。仅1例尿路上皮癌组织中检测到人NDF基因过表达，无1例肿瘤组织中c-erbB-2基因过表达。HER4基因在所有正常肾组织中均有表达，而在肿瘤组织中未见表达。在人NDF过表达的肿瘤组织中，c-erbB-2基因的表达低于正常肾组织。这些结果提示，人NDF和c-erbB-2基因介导的自分泌机制不是肾癌增殖和发展所必需的。

Expression of c-erbB-2 and human NDF gene were investigated in patients with urothelial carcinoma. Southern blot hybridization analysis demonstrated amplification of c-erbB-2 gene in 2 (6.3%) of 32 urothelial carcinomas, but neither amplification nor rearrangement of human NDF gene in the tumors. Single strand conformational polymorphism analysis (SSCP) was carried out for exon 4 to exon 9 of p53 gene to investigate whether alteration of p53 gene affected the occurrence of the amplification of c-erbB-2 gene. SSCP demonstrated 9 (28.1%) point mutations of p53 gene, while only 1 tumor have a simultaneous c-erbB-2 gene amplification, suggesting that mutation of p53 gene is not necessary for amplification of c-erbB-2 gene.C-erbB-2 gene was overexpressed in 10 (31.0%) of 32 urothelial carcionoma, while human NDF gene was expressed in normal bladder tissue, bladder tumor and human bladder cancer cell lin (5637) in a low degree. These data suggest that occurrence and progression of urothelial carcinoma was promoted through autocrine mechanism mediated by human NDF and c-erbB-2 gene.It has been demonstrated that a receptor type cellular membrane protein HER4 is necessary for activation of c-erbB-2 protein. Expression of human NDF,c-erbB-2 and HER4 genes was studied in 20 patients with renal cell carcinoma. Overexpression of human NDF gene was detected in only one urothelial carcinoma, while none of the tumors had overexpression of c-erbB-2 gene. HER4 gene was expressed in all normal renal tissues, but not in tumor tissues. In the tumor with overexpression of human NDF,the c-erbB-2 gene expression was lower than that in normal renal tissues. These data suggests that autocrine mechanism mediated by human NDF and c-erbB-2 genes is not necessary for proliferation and progression or renal cell carcinoma.