Dexamethasone down-regulates ABCG2 expression levels in breast cancer cells |
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Authors: | Honorat Mylène Mesnier Aurélia Di Pietro Attilio Lin Valérie Cohen Pascale Dumontet Charles Payen Léa |
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Affiliation: | a Université de Lyon, Lyon1, Lyon, F-69008, France b INSERM U590, Université Lyon 1, Laboratoire de cytologie analytique, Rockefeller, 8, Avenue Rockefeller, Lyon F-69008, France c Centre Léon Bérard, FNCLCC, Lyon, F-69008, France d IBCP, UMR 5086 CNRS, Université de Lyon, Lyon, F-69007, France e School of Biological Sciences, Nanyang Technological University, Singapore |
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Abstract: | The breast cancer resistance protein ABCG2 effluxes a variety of drugs and is believed to play an important role in multidrug resistance to chemotherapy. We show here for the first time that dexamethasone (DEX) and progesterone (PROG) are able to strongly inhibit ABCG2 expression in progesterone receptor (PR)-positive MCF7 and PR-negative MDA-MB-231 breast cells. In contrast, in the latter cells stably-transfected with progesterone receptor isoforms A and B, ABCG2 expression was strongly up-regulated by DEX and PROG. In addition, two other ligands of Pregnane X Receptor (PXR) and/or Glucocorticoid Receptor (GR) were also able to down-regulate ABCG2 expression in PXR- and GR-positive MCF7 cells. ABCG2 expression regulation by DEX likely resulted from the activation of PR-, PXR-, and/or GR-signaling pathways. ABCG2 expression inhibition by DEX was associated with increased sensitivity to mitoxantrone, a known ABCG2 substrate. The findings suggest that DEX may be useful in improving drug efficacy under certain conditions. |
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Keywords: | ABC, ATP-Binding Cassette BCRP/ABCG2, breast cancer resistance protein CHX, cycloheximide DEX, dexamethasone E2, estrogen GRE, glucocortocoid-response element MIT, mitoxantrone PCN, pregnenolone 16α-carbonitrile PROG, progesterone PR, progesterone receptor PRA or PRB, progesterone receptor A or B PRE, progesterone-response element ERE, estrogen-response element PXR, Pregnane X Receptor QRT-PCR, quantitative real-time polymerase chain reaction |
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