Background: Members of Human Epidermal Growth
Factor Receptors are over-expressed in variety of cancers. The EGFR-mediated activation of signal transduction pathways ultimately induce cellular growth, supress apoptosis and can cause tumor malignancy. On the contrary, TNF-α induces the expression of numerous genes which contribute to the inhibition of growth and the induction of apoptosis. Therefore, we tested the impact of EGF on TNF-α-induced expression of Caspase-1, activation of STAT1 and induction of apoptosis on human cervical carcinoma cells, (ME180).
Results: Treatment of ME180 cells with TNF-α (10 ng/ml) induced the expression of Caspase-1 in a time dependent manner. Also, pre-treatment of these cells with EGF (10ng/ml) completely inhibited
TNF-induced Caspase-1 induction. Since Caspase-1 induction is mediated by
STAT1, the levels of STAT1 activation by
TNF was determined. It was found that TNF induces STAT1 activation in these cells. However, pre-treatment of ME180 cells with EGF completely inhibited TNF-α-mediated activation of STAT1. Parallel to these findings, pre-treatment of ME180 cells with EGF for 1 hour completely inhibited TNF-induced apoptosis in these cells.
Conclusion: These results suggest that tumor microenvironment created by the tumor or surrounding cells are important in controlling the growth and apoptosis of cancer cells. Therefore, abundance of growth factors and pro-apoptotic cytokines may determine the fate of tumor behavior.
Citation Format: Osman N. Ozes. Human Epidermal Growth Factor (EGF) supresses Tumor Necrosis Factor-a (TNF-a)-mediated induction of Caspase-1, STAT1 and Apoptosis in human cervical carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4269. doi:10.1158/1538-7445.AM2013-4269