Physiological Stree-Induced Drug Resistance and Its Reversal

摘要

Physiologic induced drug resistance to topoisomerase II inhibitors was studied in EMT6 mouse mammary tumor cell lines created under the award. EMT6 cells transfected with ponasterone A inducible plasmids containing either the p65 subunit of NFkB or the p50 subunit of NEkE or the non-phosphorylatable mutant of IkE were assessed for NEkE activation and drug resistance in the presence or absence of stress. Expression of the p65 or p50 subunits resulted in drug resistance to etoposide and doxorubicin. Expression of the IkE mutant which prevents the activation of NEkE blocked the development of stress induced drug resistance. These data demonstrate that NEkE is necessary and sufficient for the development of stress induced resistance.