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 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Breast Neoplasms

diagnosis

genetics

pathology

Carcinoma

diagnosis

genetics

pathology

Cell Movement

drug effects

genetics

Cell Proliferation

Cyclin D1

antagonists & inhibitors

genetics

metabolism

physiology

Down-Regulation

drug effects

genetics

physiology

Female

Gene Expression Profiling

Gene Expression Regulation

Neoplastic

physiology

Humans

Microarray Analysis

Neoplasm Invasiveness

Oncogenes

genetics

physiology

Prognosis

RNA

Small Interfering

pharmacology

Tumor Cells

Cultured

Tumor Markers

Biological

genetics

metabolism

physiology

Up-Regulation

Publication and Content Type

ref (subject category)

art (subject category)