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 induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). 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 with BBN treatment. Epidermal growth factor (EGF) receptor mRNA was hardly affected by the treatment; while mRNA for fibroblast 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, NBT-II, expressed both TGF-alpha and c-met mRNAs, and 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.
Inui
M
M
Department of Urology, Kagawa Medical School, Japan.
Nishi
N
N
Yasumoto
A
A
Takenaka
I
I
Miyanaka
H
H
Matsumoto
K
K
Nakamura
T
T
Wada
F
F
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics*
D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D016211:Transforming Growth Factor alpha; D002085:Butylhydroxybutylnitrosamine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases