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dc.contributor.authorChia, KM
dc.contributor.authorLiu, J
dc.contributor.authorFrancis, GD
dc.contributor.authorNaderi, A
dc.date.accessioned2017-05-03T14:19:53Z
dc.date.available2017-05-03T14:19:53Z
dc.date.issued2011
dc.date.modified2012-02-17T05:03:59Z
dc.identifier.issn1522-8002
dc.identifier.doi10.1593/neo.101324
dc.identifier.urihttp://hdl.handle.net/10072/42871
dc.description.abstractEstrogen receptor (ER)-negative breast cancer is heterogeneous, and the biology of this disease has remained poorly understood. Molecular apocrine is a subtype of ER-negative breast cancer that is characterized by the overexpression of steroid-response genes such as AR and a high rate of ErbB2 amplification. In this study, we have identified a positive feedback loop between the AR and extracellular signal-regulated kinase (ERK) signaling pathways in molecular apocrine breast cancer. In this process, AR regulates ERK phosphorylation and kinase activity. In addition, AR inhibition results in the down-regulation of ERK target proteins phospho-RSK1, phospho-Elk-1, and c-Fos using an in vivo molecular apocrine model. Furthermore, we show that AR-mediated induction of ERK requires ErbB2, and AR activity, in turn, regulates ErbB2 expression as an AR target gene. These findings suggest that ErbB2 is an upstream connector between the AR and ERK signaling pathways. Another feature of this feedback loop is an ERK-mediated regulation of AR. In this respect, the inhibition of ERK phosphorylation reduces AR expression and CREB1-mediated transcriptional regulation of AR acts as a downstream connector between the AR and ERK signaling pathways in molecular apocrine cells. Finally, we demonstrate that AR-positive staining is associated with the overexpression of ERK signaling targets phospho-Elk-1 and c-Fos in ER-negative breast tumors, which further supports a cross-regulation between the AR and ERK signaling pathways in molecular apocrine subtype. This study demonstrates an AR-ERK feedback loop in ER-negative breast cancer with significant biologic and therapeutic implications in this disease.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent5096877 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherNeoplasia Press
dc.publisher.placeUnited States
dc.publisher.urihttp://www.neoplasia.com/abstract.php?msid=3937
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom154
dc.relation.ispartofpageto166
dc.relation.ispartofissue2
dc.relation.ispartofjournalNeoPlasia
dc.relation.ispartofvolume13
dc.rights.retentionY
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3202
dc.titleA Feedback Loop between Androgen Receptor and ERK Signaling in Estrogen Receptor-Negative Breast Cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2011 Neoplasia Press. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2011
gro.hasfulltextFull Text
gro.griffith.authorFrancis, Glenn D.


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