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Gefitinib ('Iressa', ZD1839) inhibits the growth response of bladder tumour cell lines to epidermal growth factor and induces TIMP2

Lookup NU author(s): Dr Joyce Nutt, Henry Lazarowicz, Kilian Mellon, Professor John LunecORCiD


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The effect of EGF stimulation and its inhibition with gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been investigated in two EGFR-positive human bladder tumour cell lines, RT112 and RT4. The growth of RT112 cells in a medium containing 10% foetal bovine serum was inhibited by 50% with 10 μM gefitinib, whereas this dose completely inhibited RT4 cell growth. Cells were more sensitive to growth inhibition in the serum-free medium. Increased growth of cells in the serum-free medium was observed with 10 or 50 ng ml-1 EGF and the proliferative effect of EGF stimulation in both cell lines was inhibited in the presence of 1 μM, but not 0.1 μM gefitinib. Zymography of the conditioned medium from RT112 cells treated with EGF and gefitinib showed a decrease in matrix metalloproteinase 2 (MMP2) concentrations. Western blot analysis showed that tissue inhibitor of metalloproteinase 1 (TIMP1) increased in the conditioned medium from RT112 cells treated with EGF, and this was partially inhibited with both 1 and 5 μM gefitinib. Conversely, TIMP2 decreased with EGF stimulation and this was reversed with gefitinib. Tissue inhibitor of metalloproteinase 1 had no effect on the growth of either cell line. These studies show alterations in the balance of MMPs and their inhibitors in EGF-stimulated bladder tumour cells, which are reversed by gefitinib, suggesting gefitinib should be investigated for its effect on human bladder tumours. © 2004 Cancer Research UK.

Publication metadata

Author(s): Nutt, J., Lazarowicz, H., Mellon, J., Lunec, J.

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2004

Volume: 90

Issue: 8

Pages: 1679-1685

Print publication date: 19/04/2004

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827


DOI: 10.1038/sj.bjc.6601768

PubMed id: 15083203


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