ENHANCED GENE-EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND C-MET IN RAT URINARY-BLADDER CANCER

To investigate the roles of growth factors in bladder cancer, changes in the expression of messenger RNAs (mRNAs) for several growth factors and their receptors were examined during rat bladder carcinogenesis i nduced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Northern blo t analysis showed that the contents of mRNAs for transforming growth f actor-alpha (TGF-alpha) and c-met/hepatocyte growth factor (HGF) recep tor increased with BBN treatment. Epidermal growth factor (EGF) recept or mRNA was hardly affected by the treatment; while mRNA for fibroblas t growth factor (FGF) receptor 1 and transforming growth factor-beta ( TGF-beta) type II receptor decreased with BBN treatment. A rat bladder tumor cell line, NET-II, expressed both TGF-alpha and c-met mRNAs, an d HGF showed apparent scattering and growth-stimulating effects on the cells. These results indicate the possibility that TGF-alpha produced by a bladder cancer, in addition to urinary EGF, plays a role in the development of bladder cancer, and that enhanced cell motility due to activation of the c-met/HGF receptor participates in the invasion and metastasis of the cancer cells.