RT Journal Article SR Electronic T1 Antiproliferative Effects of Gefitinib are Associated with Suppression of E2F-1 Expression and Telomerase Activity JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3387 OP 3391 VO 26 IS 5A A1 MITSUHIRO SUENAGA A1 AKIHIKO YAMAGUCHI A1 HIROSHI SODA A1 KOJI ORIHARA A1 YUICHI TOKITO A1 YOSHIMUNE SAKAKI A1 MEGUMI UMEHARA A1 KENJI TERASHI A1 NAKAAKI KAWAMATA A1 MIKIO OKA A1 SHIGERU KOHNO A1 CHUWA TEI YR 2006 UL http://ar.iiarjournals.org/content/26/5A/3387.abstract AB Background: Gefitinib (Iressa, ZD1839) is a selective epidermal growth factor receptor tyrosine kinase inhibitor. E2F-1 is a critical determinant in cell cycle. Growth signals up-regulate telomerase activity. The effects of gefitinib on E2F-1 and telomerase in A549, H23 and A431 cells were examined. Materials and Methods: Cell proliferation and cell cycle progression were measured by the WST-1 assay and flow cytometry. The expression of E2F-1 and cyclin-dependent kinase inhibitors was evaluated, and hTERT mRNA expression and telomerase activity were analyzed. Results: In the A431 and A549 cells, treatment with gefitinib inhibited cell proliferation and was associated with an increase in G1-phase. In both cell types, gefitinib decreased the expression of E2F-1 mRNA and protein, followed by the suppression of hTERT mRNA and telomerase activity. In the H23 cells, gefitinib did not affect cell proliferation. Conclusion: The antiproliferative effects of gefitinib may be, at least in part, due to the inhibition of E2F-1 expression and telomerase activity. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved