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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Sophie Lehn
  • Nicholas P Tobin
  • Pontus Berglund
  • Kristina Nilsson
  • Andrew H Sims
  • Karin Jirström
  • Pirkko Härkönen
  • Rebecca Lamb
  • Göran Landberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)2886-2897
JournalAmerican Journal of Pathology
Volume177
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology (Malmö) (013031000), Experimental Pathology (013031100), Tumour Biology, Malmö (013031300), Pathology, (Lund) (013030000) Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:29.

Related research output

Sophie Lehn, 2013, Department of Laboratory Medicine, Lund University. 93 p.

Research output: ThesisDoctoral Thesis (compilation)

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