MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors
The ATP-binding cassette multidrug resistance protein 8 (MRP8/ABCC11) mediates the excretion of anticancer drugs. ABCC11 mRNA and protein levels were enhanced by DEX (dexamethasone) and by PROG (progesterone) in MCF7 (progesterone receptor-(PR-) positive) but not in MDA-MB-231 (PR-negative) breast c...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | International Journal of Breast Cancer |
| Online Access: | http://dx.doi.org/10.4061/2011/807380 |
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| author | Mylène Honorat Aurélia Mesnier Julie Vendrell Attilio Di Pietro Valérie Lin Charles Dumontet Pascale Cohen Léa Payen |
| author_facet | Mylène Honorat Aurélia Mesnier Julie Vendrell Attilio Di Pietro Valérie Lin Charles Dumontet Pascale Cohen Léa Payen |
| author_sort | Mylène Honorat |
| collection | DOAJ |
| description | The ATP-binding cassette multidrug resistance protein 8 (MRP8/ABCC11) mediates the excretion of anticancer drugs. ABCC11 mRNA and protein levels were enhanced by DEX (dexamethasone) and by PROG (progesterone) in MCF7 (progesterone receptor-(PR-) positive) but not in MDA-MB-231 (PR-negative) breast cancer cells. This suggested a PR-signaling pathway involvement in ABCC11 regulation. Nevertheless, pregnenolone-16α-carbonitrile (GR antagonist) and clotrimazole strongly and moderately decreased ABCC11 expression levels in Glucocortocoid Receptor-(GR-) and Pregnane X Receptor (PXR)-positive MCF7 cells but not in MDA-MB-231 cells (GR- and PXR-positive). Thus, GR-signaling pathway involvement could not be excluded in ABCC11 regulation in MCF7 cells. Furthermore, ABCC11 levels were positively correlated with the PR status of postmenopausal patient breast tumors from two independent cohorts. Thus, in the subclass of breast tumors (Estrogen Receptor-(ER-) negative/PR-positive), the elevated expression level of ABCC11 may alter the sensitivity to ABCC11 anticancer substrates, especially under treatment combinations with DEX. |
| format | Article |
| id | doaj-art-f2d5474b1d5540e793ce36ec33a2f51d |
| institution | Kabale University |
| issn | 2090-3189 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Breast Cancer |
| spelling | doaj-art-f2d5474b1d5540e793ce36ec33a2f51d2025-02-03T01:20:26ZengWileyInternational Journal of Breast Cancer2090-31892011-01-01201110.4061/2011/807380807380MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast TumorsMylène Honorat0Aurélia Mesnier1Julie Vendrell2Attilio Di Pietro3Valérie Lin4Charles Dumontet5Pascale Cohen6Léa Payen7Université de Lyon, Lyon1, Lyon 69008, FranceUniversité de Lyon, Lyon1, Lyon 69008, FranceUniversité de Lyon, Lyon1, Lyon 69008, FranceEquipe Labellisée Ligue 2009, Institut de Biologie et Chimie des Protéines FR 3302, BM2SI, UMR 5086/Université Lyon 1, IFR128 BioSciences Gerland, 69367 Lyon Cedex 07, FranceSchool of Biological Sciences, Nanyang Technological University, 637616, SingaporeUniversité de Lyon, Lyon1, Lyon 69008, FranceUniversité de Lyon, Lyon1, Lyon 69008, FranceUniversité de Lyon, Lyon1, Lyon 69008, FranceThe ATP-binding cassette multidrug resistance protein 8 (MRP8/ABCC11) mediates the excretion of anticancer drugs. ABCC11 mRNA and protein levels were enhanced by DEX (dexamethasone) and by PROG (progesterone) in MCF7 (progesterone receptor-(PR-) positive) but not in MDA-MB-231 (PR-negative) breast cancer cells. This suggested a PR-signaling pathway involvement in ABCC11 regulation. Nevertheless, pregnenolone-16α-carbonitrile (GR antagonist) and clotrimazole strongly and moderately decreased ABCC11 expression levels in Glucocortocoid Receptor-(GR-) and Pregnane X Receptor (PXR)-positive MCF7 cells but not in MDA-MB-231 cells (GR- and PXR-positive). Thus, GR-signaling pathway involvement could not be excluded in ABCC11 regulation in MCF7 cells. Furthermore, ABCC11 levels were positively correlated with the PR status of postmenopausal patient breast tumors from two independent cohorts. Thus, in the subclass of breast tumors (Estrogen Receptor-(ER-) negative/PR-positive), the elevated expression level of ABCC11 may alter the sensitivity to ABCC11 anticancer substrates, especially under treatment combinations with DEX.http://dx.doi.org/10.4061/2011/807380 |
| spellingShingle | Mylène Honorat Aurélia Mesnier Julie Vendrell Attilio Di Pietro Valérie Lin Charles Dumontet Pascale Cohen Léa Payen MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors International Journal of Breast Cancer |
| title | MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors |
| title_full | MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors |
| title_fullStr | MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors |
| title_full_unstemmed | MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors |
| title_short | MRP8/ABCC11 Expression Is Regulated by Dexamethasone in Breast Cancer Cells and Is Associated to Progesterone Receptor Status in Breast Tumors |
| title_sort | mrp8 abcc11 expression is regulated by dexamethasone in breast cancer cells and is associated to progesterone receptor status in breast tumors |
| url | http://dx.doi.org/10.4061/2011/807380 |
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