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

c-erbB-2及其配体影响泌尿系统癌恶性潜能的意义。

• 批准号: 05454430
• 负责人: KATO Tetsuro
• 金额: $ 4.03万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454430/
• 关键词: bladder carcinoma; c-erbB-2; human NDF; renal cell carcinoma; HER-4; EGFR family; urothelial carcinoma; renal cell carcinoma; heregulin; neu differentiation factor; urogenital cancer; urinary bladder cancer; renal cell cancer

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.

研究了c-erbB-2和NDF基因在尿路上皮癌患者中的表达。Southern blot杂交分析显示，32例尿路上皮癌中2例（6.3%）存在c-erbB-2基因扩增，但在肿瘤中未发现人NDF基因扩增或重排。对p53基因外显子4 ~ 9进行单链构象多态性分析（SSCP），探讨p53基因的改变是否影响c-erbB-2基因扩增的发生。SSCP出现p53基因的9个点突变（28.1%），而只有1个肿瘤同时出现c-erbB-2基因扩增，提示p53基因突变不需要c-erbB-2基因扩增。32例尿路上皮癌中10例（31.0%）c-erbB-2基因过表达，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）中低程度表达。这些数据表明，尿路上皮癌的发生和发展是通过人NDF和c-erbB-2基因介导的自分泌机制促进的。已经证明，受体型细胞膜蛋白HER4是c-erbB-2蛋白激活所必需的。研究了20例肾细胞癌患者NDF、c-erbB-2和HER4基因的表达。只有1例尿路上皮癌中检测到人NDF基因过表达，而c-erbB-2基因均未过表达。HER4基因在所有正常肾组织中均有表达，而在肿瘤组织中无表达。在人NDF过表达的肿瘤中，c-erbB-2基因表达低于正常肾组织。这些数据表明，由人类NDF和c-erbB-2基因介导的自分泌机制在肾细胞癌的增殖和进展中不是必需的。

项目成果

佐藤一成: "泌尿器癌における癌遺伝子の活性化と臨床的意義 -とくにc-erbB-2を中心として-" 日泌尿会誌. 85. 57-59 (1994)

Kazunari Sato：“泌尿系癌症中癌基因的激活和临床意义 - 特别关注 c-erbB-2”日本泌尿外科学会杂志 85. 57-59 (1994)。

佐藤,一成: "泌尿器癌におけるhuman NDF,c-erbB-2およびHER4の発現" 第30回日本癌治療学会総会抄録号. 29. 160 (1994)

Kazunari Sato：“泌尿系癌症中人 NDF、c-erbB-2 和 HER4 的表达”第 30 届日本癌症治疗学会年会，摘要第 29. 160 号（1994 年）

Sato, K.: "Urinary Bladder Cancer" Molecular Medicine. (in press). (1996)

Sato, K.：“膀胱癌”分子医学。

佐藤一成: "膀胱癌" Molecular Medicine,. (印刷中).

Kazunari Sato：“膀胱癌”分子医学（正在出版）。

佐藤一成: "膀胱癌" Molecular Medicine. (印刷中). (1996)

Kazunari Sato：“膀胱癌”分子医学（出版中）。