Down-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features

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 G(0)/G(1) 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 be tween 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 con firmed 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 (Am J Pathol 2010 177 2886-2897 DOI 10 2393/ajpath 2010.100303)