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

为了探讨生长因子在膀胱癌中的作用，我们检测了n -丁基- n -（4-羟基丁基）亚硝胺（BBN）诱导大鼠膀胱癌过程中几种生长因子及其受体mrna的表达变化和临床标本。Northern blot分析显示，在BBN处理下，转化生长因子- α (tgf - α)和c-met/肝细胞生长因子（HGF）受体mRNA含量升高，表皮生长因子（EGF）受体mRNA含量略有升高。而成纤维细胞生长因子（FGF）受体1和转化生长因子（tgf - β） II型受体的表达在BBN治疗后下降。其他因子（EGF、bFGF、KGF、HGF、tgf - β 1） mrna含量几乎不受治疗影响或低于可检测水平。6例膀胱肿瘤标本中c-met mRNA含量均较高，tgf - α mRNA含量不高。一个大鼠膀胱肿瘤细胞系NBT-II同时表达tgf - α和c-met mrna， HGF对细胞表现出明显的散射和促生长作用。人膀胱肿瘤细胞系（UM-UC-3和T-24）也易受HGF的细胞散射作用。这些结果表明，除了尿EGF外，膀胱癌产生的tgf - α可能在大鼠膀胱癌的发生发展中发挥作用，并且由于c-met/HGF受体的激活而增强的细胞运动性参与了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.