Changes in gene activity of growth factors and their receptorsand the contentsof growth factors in urine during bladder carcinogenesis.

膀胱癌发生过程中生长因子及其受体基因活性及尿液中生长因子含量的变化

• 批准号: 06671595
• 负责人: NISHI Nozomu
• 金额: $ 1.34万
• 依托单位: Kagawa Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671595/
• 关键词: Bladder carcinoma; Growth factors; Growth factor receptors; Metastasis; Cell motility; HGF; c-met; TGF-alpha

To investigate the roles of growth factors in bladder cancer, changes in expression of mRNAs for several growth factors and their receptors were examined during rat bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) and in clinical specimens. Northern blot analysis showed that the contents of mRNAs for transforming growth factor-alpha (TGF-alpha) and c-met/hepatocyte growth factor (HGF) receptor increased on BBN treatment, Epidermal growth factor (EGF) receptor mRNA was slightly increased with the treatment. While those for fibroblast growth factor (FGF) receptor 1 and transforming growth factor beta (TGF-beta) type II receptor decreased on BBN treatment. The contents of mRNAs for the other factors investigated (EGF,bFGF,KGF,HGF,TGF-beta1) were hardly affected with the treatment or below detectable level. In case of human bladder specimens, the content of c-met mRNA but not TGF-alpha mRNA was high in all the tumor tissues (6 specimens) examined. A rat bladder tumor cell line, NBT-II,expressed both TGF-alpha and c-met mRNAs, and HGF showed apparent scattering and growth stimulating effects on the cells. Human bladder tumor cell lines (UM-UC-3 and T-24) were also susceptible to the cell scattering action of HGF.These results indicate the possibilities that TGF-alpha produced by a bladder cancer in addition to urinary EGF play a role in the development of rat bladder cancer, and that enhanced cell motility due to activation of the c-met/HGF receptor participates in the invasion and metastasis of both rat and human bladder cancer cells.

为探讨生长因子在膀胱癌发生中的作用，检测了几种生长因子及其受体在N-butyl-N-（4-hydroxybutyl）nitrosamine（BBN）诱发大鼠膀胱癌过程中及临床标本中的表达变化。北方印迹分析显示，BBN处理后，转化生长因子-α（TGF-α）和c-met/肝细胞生长因子（HGF）受体mRNA含量增加，表皮生长因子（EGF）受体mRNA含量略有增加。而BBN处理后，成纤维细胞生长因子（FGF）受体1和转化生长因子β（TGF-β）II型受体的表达降低。研究的其他因子（EGF、bFGF、KGF、HGF、TGF-β 1）的mRNA含量几乎不受治疗影响或低于可检测水平。在人膀胱标本的情况下，在所有检查的肿瘤组织（6个标本）中，c-met mRNA的含量高，而TGF-α mRNA的含量低。大鼠膀胱肿瘤细胞系NBT-II表达TGF-α和c-met mRNA，HGF对细胞表现出明显的散射和生长刺激作用。人膀胱肿瘤细胞系（UM-UC-3和T-24）也对HGF的细胞散射作用敏感。这些结果表明，除了尿EGF之外，膀胱癌产生的TGF-α在大鼠膀胱癌的发展中起作用的可能性，并且由于c-met/c-met的激活而增强了细胞运动性。HGF受体参与大鼠和人膀胱癌细胞的侵袭和转移。

项目成果

Nishi Nozomu: "Western blot analysis of epidermal growth factor using gelatin-coated polyvinylidene difluoride membranes." Anal.Biochem.227. 401-402 (1995)

Nishi Nozomu：“使用明胶涂层的聚偏二氟乙烯膜对表皮生长因子进行蛋白质印迹分析。”

Nishi Nozomu: "Identification of probasin-related antigen as cystathionine γ-lyase by molecular cloning." J.Biol.Chem.269. 1015-1019 (1994)

Nishi Nozomu：“通过分子克隆将 probasin 相关抗原鉴定为胱硫醚 γ-裂解酶。”J.Biol.Chem.269（1994）。

Inui Masashi: "Enhanced gene expression of transforming growth factor-alpha and c-met in rat urinary bladder cancer." Urol.Res.(in press).

Inui Masashi：“大鼠膀胱癌中转化生长因子-α 和 c-met 的基因表达增强。”

Nishi Nozomu: "Identification of probasin-related antigen as cystathionine gamma-lyase by molecular cloning." j.Biol.Chem.269. 1015-1019 (1994)

Nishi Nozomu：“通过分子克隆将 probasin 相关抗原鉴定为胱硫醚 γ-裂解酶。”

Inui Masashi: "Enhanced gene expression of transforming growth factor-α and c-met in rat urinary bladder cancer." Urol.Res.(in press).

Inui Masashi：“大鼠膀胱癌中转化生长因子-α 和 c-met 的基因表达增强。”（正在出版）。