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

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。

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.