The role of C/EBP-β LIP in multidrug resistance

Journal of the National Cancer Institute
Chiara RigantiMenachem Rubinstein

Abstract

Chemotherapy triggers endoplasmic reticulum (ER) stress, which in turn regulates levels of the active (LAP) and the natural dominant-negative (LIP) forms of the transcription factor C/EBP-β. LAP upregulates and LIP downregulates the multidrug resistance (MDR) protein P-glycoprotein (Pgp), but it is not known how critical is their role in establishing MDR. Cell viability was quantitated by crystal violet staining and measuring absorbance at 540nm. Expression of various proteins was determined by immunoblotting. mRNA levels were determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). LIP and LAP were overexpressed using expression plasmids followed by selection with blasticidin. Tumor cells expressing doxycycline-inducible LIP were orthotopically implanted in mice (n = 15 mice per group), and tumor size was measured daily by caliper. Tumor sections were stained with hematoxylin and eosin and immunostained for Pgp, proliferation, and ER stress markers. MDR cells do not express basal, chemotherapy-triggered, or ER stress-triggered LIP and fail to activate the CHOP-caspase-3 death-triggering axis upon ER stress or chemotherapy challenge. Overexpression of LIP reversed the MDR phenotype in vitro and in tu...Continue Reading

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Citations

Apr 28, 2016·Journal of Medicinal Chemistry·Konstantin ChegaevAlberto Gasco
Apr 7, 2017·Cell Death & Disease·Rina Wassermann-Dozorets, Menachem Rubinstein
Feb 9, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Milan HanoZdena Sulová
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Aug 10, 2021·Angewandte Chemie·Sierra C MarkerJustin J Wilson
Sep 28, 2021·Nano Letters·Rong Sheng LiCheng Zhi Huang

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