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dc.contributor.authorLehn, Sophie
dc.contributor.authorTobin, Nicholas P
dc.contributor.authorBerglund, P
dc.contributor.authorNilsson, K
dc.contributor.authorSims, A H
dc.contributor.authorJirström, K
dc.contributor.authorHärkönen, P
dc.contributor.authorLamb, Rebecca
dc.contributor.authorLandberg, Göran
dc.date.accessioned2010-11-17T12:40:57Z
dc.date.available2010-11-17T12:40:57Z
dc.date.issued2010-10-22
dc.identifier.citationDown-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features. 2010: Am J Patholen
dc.identifier.issn1525-2191
dc.identifier.pmid20971731
dc.identifier.doi10.2353/ajpath.2010.100303
dc.identifier.urihttp://hdl.handle.net/10541/115708
dc.description.abstractThe oncogene cyclin D1 is highly expressed in many breast cancers and, despite its proliferation-activating properties, it has been linked to a less malignant phenotype. To clarify this observation, we focused on two key components of malignant behavior, migration and proliferation, and observed that quiescent G0/G1 cells display an increased migratory capacity compared to cycling cells. We also found that the down-regulation of cyclin D1 in actively cycling cells significantly increased migration while also decreasing proliferation. When analyzing a large set of premenopausal breast cancers, we observed an inverse proliferation-independent link between cyclin D1 and tumor size and recurrence, suggesting that this protein might abrogate infiltrative malignant behavior in vivo. Finally, gene expression analysis after cyclin D1 down-regulation by siRNA confirmed changes in processes associated with migration and enrichment of our gene set in a metastatic poor prognosis signature. This novel function of cyclin D1 illustrates the interplay between tumor proliferation and migration and may explain the attenuation of malignant behavior in breast cancers with high cyclin D1 levels.
dc.languageENG
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectOncogene Cyclin D1en
dc.titleDown-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features.en
dc.typeArticleen
dc.contributor.departmentFrom the Center for Molecular Pathology, Department of Laboratory Medicine,* Lund University, UMAS, Sweden; the Breakthrough Breast Cancer Research Unit, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Manchester, United Kingdom; Applied Bioinformatics of Cancer, Breakthrough Breast Cancer Research Unit, Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom; Tumor Biology, the Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden; and the Department of Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.en
dc.identifier.journalThe American Journal of Pathologyen
html.description.abstractThe oncogene cyclin D1 is highly expressed in many breast cancers and, despite its proliferation-activating properties, it has been linked to a less malignant phenotype. To clarify this observation, we focused on two key components of malignant behavior, migration and proliferation, and observed that quiescent G0/G1 cells display an increased migratory capacity compared to cycling cells. We also found that the down-regulation of cyclin D1 in actively cycling cells significantly increased migration while also decreasing proliferation. When analyzing a large set of premenopausal breast cancers, we observed an inverse proliferation-independent link between cyclin D1 and tumor size and recurrence, suggesting that this protein might abrogate infiltrative malignant behavior in vivo. Finally, gene expression analysis after cyclin D1 down-regulation by siRNA confirmed changes in processes associated with migration and enrichment of our gene set in a metastatic poor prognosis signature. This novel function of cyclin D1 illustrates the interplay between tumor proliferation and migration and may explain the attenuation of malignant behavior in breast cancers with high cyclin D1 levels.


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