4.7 Article

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

Journal

BRITISH JOURNAL OF CANCER
Volume 90, Issue 8, Pages 1679-1685

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6601768

Keywords

gefitinib; epidermal growth factor receptor; bladder cell lines; MMPs; TIMPs

Categories

Ask authors/readers for more resources

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 muM 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 muM, but not 0.1 muM 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 muM 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available