Down-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features.
Authors
Lehn, SophieTobin, Nicholas P
Berglund, P
Nilsson, K
Sims, A H
Jirström, K
Härkönen, P
Lamb, Rebecca
Landberg, Göran
Affiliation
From 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.Issue Date
2010-10-22
Metadata
Show full item recordAbstract
The 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.Citation
Down-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features. 2010: Am J PatholJournal
The American Journal of PathologyDOI
10.2353/ajpath.2010.100303PubMed ID
20971731Type
ArticleLanguage
enISSN
1525-2191ae974a485f413a2113503eed53cd6c53
10.2353/ajpath.2010.100303
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