Carcinogenesis, Vol. 21, No. 12, 2211-2218,
December 2000
© 2000 Oxford University Press
CANCER BIOLOGY |
Involvement of epidermal growth factor receptor in chemically induced mouse bladder tumour progression
UMR 144, CNRS, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
This study was designed to investigate the role of the epidermal growth factor receptor (EGFR) and its ligands in chemically induced mouse bladder cancer. Bladder tumours were induced in C57Bl/6 and B6D2F1 mice by treatment with the carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). The levels of mRNA for EGFR and its ligands were analysed by reverse transcription–polymerase chain reaction (RT–PCR) in bladder tumours and in normal bladder urothelia. EGFR mRNA was detected in all tumours, transforming growth factor 
(TGF) mRNA levels were similar to those in normal bladder urothelia or were decreased and mRNA levels for amphiregulin, heparin-binding epidermal growth factor-like factor (HB-EGF) and betacellulin were significantly higher than those in normal urothelia. Seven cell lines were derived from chemically induced tumours. These cell lines were able to grow in serum-free conditions. All the cell lines tested expressed the genes encoding EGFR and at least one of its ligands. Proliferation of these cell lines was inhibited by AG1478, a specific EGFR tyrosine kinase inhibitor, strongly suggesting that EGFR was involved in cell growth. As expected, EGFR was found to be phosphorylated in serum-free medium, this phosphorylation being inhibited by AG1478. Conditioned medium of a bladder cancer cell line had EGFR-stimulating activity and an antibody directed against EGFR inhibited proliferation by 45%. This suggests that tumour cell growth is stimulated by an autocrine loop involving EGFR and secreted growth factors. AG1478 decreased the expression of genes for amphiregulin, HB-EGF and betacellulin, showing that EGFR activation induces up-regulation of the EGFR ligands. These results suggest that EGFR plays a critical role in bladder tumour progression.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. M. Kooter, J. L. A. Pennings, P. H. B. Fokkens, D. L. A. C. Leseman, A. J. F. Boere, M. E. Gerlofs-Nijland, F. R. Cassee, J. A. C. Schalk, T. J. H. Orzechowski, M. M. Schaap, et al. Ozone induces clear cellular and molecular responses in the mouse lung independently of the transcription-coupled repair status J Appl Physiol, March 1, 2007; 102(3): 1185 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jin, K. K. Iwata, A. Belldegrun, R. Figlin, A. Pantuck, Z.-F. Zhang, R. Lieberman, and J. Rao Effect of an epidermal growth factor receptor tyrosine kinase inhibitor on actin remodeling in an in vitro bladder cancer carcinogenesis model. Mol. Cancer Ther., July 1, 2006; 5(7): 1754 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nicolle, A. Daher, P. Maille, M. Vermey, S. Loric, A. Bakkar, H. Wallerand, D. Vordos, F. Vacherot, S. G. D. de Medina, et al. Gefitinib Inhibits the Growth and Invasion of Urothelial Carcinoma Cell Lines in which Akt and MAPK Activation Is Dependent on Constitutive Epidermal Growth Factor Receptor Activation. Clin. Cancer Res., May 1, 2006; 12(9): 2937 - 2943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Lubet, K. Huebner, L. Y.Y. Fong, D. C. Altieri, V. E. Steele, L. Kopelovich, C. Kavanaugh, M.M. Juliana, S.-j. Soong, and C. J. Grubbs 4-Hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers in mice: characterization of FHIT and survivin expression and chemopreventive effects of indomethacin Carcinogenesis, March 1, 2005; 26(3): 571 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, J. Lee, M. Cooley, E. Bhogte, S. Hartley, and A. Glick Smad7 but not Smad6 Cooperates with Oncogenic ras to Cause Malignant Conversion in a Mouse Model for Squamous Cell Carcinoma Cancer Res., November 15, 2003; 63(22): 7760 - 7768. [Abstract] [Full Text] [PDF]
|
|