Abstract 684: The difference between gefitinib and serum deprivation in cancer cells

Abstract

Abstract Gefitinib is a selective inhibitor of epidermal growth factor receptor tyrosine kinase. The serum free condition could resemble to gefitinib exposure since it blocks EGF stimuli. In this study, we examined distinction between gefitinib exposure and serum deprivation in cultured cancer cells. At first, we verified that ERK phosphorylation was downregulated by gefitinib exposure in A431 and A549 cells. We examined the phosphorylation status of ERK under the serum deprivation condition. The phosphorylation of ERK in A431 cells was downregulated after 1hr culture in serum free medium, while after 3-6hr ERK was phosphorylated again. We hypothesized that an auto- or paracrine mechanism would work to phosphorylate ERK. In the cells cultured with the conditioned serum free medium from the dish in which A431 cultured for 24hr, the downregulation of ERK phosphorylation was weaker than with the fresh serum free medium. We confirmed that gefitinib could inhibit the ERK phosphorylation under the serum free condition. Exogenous EGF attenuated the inhibitory effect on ERK phosphorylation with serum free medium. These results suggest EGF may be one of the auto- or paracrine substance that induces ERK phosphorylation. Since the ERK phosphorylation status affects the stability of c-MYC, we also examined whether “gefitinib” and “serum deprivation” affect the expression of c-MYC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 684. doi:10.1158/1538-7445.AM2011-684