Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma.

摘要: Malignant pleural mesothelioma (MPM) is a rare malignancy with no known curative modality. Approximately 70% of MPMs have high levels expression the epidermal growth factor receptor (EGFR), and subset cell lines derived from MPM patients express both EGFR transforming alpha, suggesting an autocrine role for in MPM. We determined effects inhibition vitro, using four previously untreated epithelial (H2461 H2591), sarcomatoid (H2373), biphasic (MSTO-211H) All expressed at comparable non-small lung carcinoma (NSCLC) line A549, as shown by Western blot analysis. ZD1839 significantly inhibited factor-dependent signaling including phosphorylation AKT extracellular signal-regulated kinases 1 2 all lines. Furthermore, treatment led to significant dose-dependent reduction colony formation (41-89% 10 microM) when cells were grown soft agarose. MSTO-211H, H2461, H2373 more sensitive growth-inhibitory than was NSCLC whereas H2591 had similar sensitivity A549. This variability not related amount present on or degree ZD1839. show that cells, which 89% microM ZD1839, undergo arrest G(1)-S phase cycle corresponding increase p27 levels. However, lines, 41% changes Our findings demonstrate effective against it A549 suggest may be therapeutic option