Jackson Nicole M, Ceresa Brian P
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, United States.
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, United States.
Exp Cell Res. 2017 Jul 1;356(1):93-103. doi: 10.1016/j.yexcr.2017.04.016. Epub 2017 Apr 19.
The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor with primary implications in cell growth in both normal and malignant tissue. Paradoxically, cell lines that hyperexpress the EGFR have been documented to undergo receptor-mediated apoptosis. The underlying mechanism by which EGF-induced apoptosis occurs however remains inexplicit. In an attempt to identify this mechanism, we assessed downstream effectors of EGFR in MDA-MB-468 cells during conditions of EGF-induced apoptosis. The effector assessment revealed STAT3 as a potential mediator of EGF-induced apoptosis. Alternative strategies for activating STAT3, independent of EGFR stimulation, resulted in the induction of the apoptotic pathways. A reduction in STAT3 expression via RNAi resulted in a significant attenuation of EGF-induced PARP cleavage. Our findings support STAT3 as a positive mediator of EGF-induced apoptosis in MDA-MB-468 cells.
表皮生长因子受体（EGFR）是一种细胞表面受体，在正常组织和恶性组织的细胞生长中都具有重要作用。矛盾的是，已有文献记载，过度表达EGFR的细胞系会经历受体介导的凋亡。然而，表皮生长因子（EGF）诱导凋亡发生的潜在机制仍不明确。为了确定这一机制，我们在EGF诱导凋亡的条件下，评估了MDA-MB-468细胞中EGFR的下游效应器。效应器评估显示，信号转导和转录激活因子3（STAT3）是EGF诱导凋亡的潜在介质。独立于EGFR刺激激活STAT3的替代策略导致了凋亡途径的诱导。通过RNA干扰降低STAT3表达导致EGF诱导的聚（ADP-核糖）聚合酶（PARP）裂解显著减弱。我们的研究结果支持STAT3作为MDA-MB-468细胞中EGF诱导凋亡的正向介质。
