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dc.contributor.authorKochel, T.J.
dc.contributor.authorReader, J.C.
dc.contributor.authorMa, X.
dc.date.accessioned2019-11-01T12:49:35Z
dc.date.available2019-11-01T12:49:35Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85010736843&doi=10.18632%2foncotarget.14145&partnerID=40&md5=3d07ea0596248079ff8dba6b443effa1
dc.identifier.urihttp://hdl.handle.net/10713/11294
dc.description.abstractCyclooxygenase-2 (COX-2) and its primary enzymatic product, prostaglandin E2 (PGE2), are associated with a poor prognosis in breast cancer. In order to elucidate the factors contributing to intratumoral PGE2 levels, we evaluated the expression of COX- 2/PGE2 pathway members MRP4, the prostaglandin transporter PGT, 15-PGDH (PGE2 metabolism), the prostaglandin E receptor EP4, COX-1, and COX-2 in normal, luminal, and basal breast cancer cell lines. The pattern of protein expression varied by cell line reflecting breast cancer heterogeneity. Overall, basal cell lines expressed higher COX-2, higher MRP4, lower PGT, and lower 15-PGDH than luminal cell lines resulting in higher PGE2 in the extracellular environment. Genetic or pharmacologic suppression of MRP4 expression or activity in basal cell lines led to less extracellular PGE2. The key finding is that xenografts derived from a basal breast cancer cell line with stably suppressed MRP4 expression showed a marked decrease in spontaneous metastasis compared to cells with unaltered MRP4 expression. Growth properties of primary tumors were not altered by MRP4 manipulation. In addition to the well-established role of high COX-2 in promoting metastasis, these data identify an additional mechanism to achieve high PGE2 in the tumor microenvironment; high MRP4, low PGT, and low 15-PGDH. MRP4 should be examined further as a potential therapeutic target in basal breast cancer.en_US
dc.description.urihttps://doi.org/10.18632/oncotarget.14145en_US
dc.language.isoen_USen_US
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotarget
dc.subjectBreast canceren_US
dc.subjectMetastasisen_US
dc.subjectMRP4en_US
dc.subjectPGE2en_US
dc.subjectTNBCen_US
dc.titleMultiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/ triple negative breast canceren_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.14145


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