Research article
Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility
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* Corresponding authors: David T Leong csiltwd@nus.edu.sg - Andre J van Wijnen andre.vanwijnen@umassmed.edu
1 Cancer Science Institute of Singapore, National University of Singapore, 28 Medical Drive, 117456 Singapore
2 Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5- 02-09, 4 Engineering Drive 4, 117576 Singapore
3 Department of Cell Biology and Cancer Center, 55 Lake Avenue North, University of Massachusetts Medical School, Worcester, MA 01655, USA
4 Current address: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 S. Paulina Street, Chicago, IL 60612, USA
5 Musculoskeletal Research Laboratories, Department of Orthopaedic Surgery, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block-Level 11, 119228 Singapore
6 Division of Musculoskeletal Oncology, Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore
7 Cancer and Stem Cell Biology Program, Duke-National University of Singapore Graduate Medical School, Khoo Teck Puat Building Level 7, 8 College Road, 169857 Singapore
8 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597 Singapore
9 Department of Pathology, National University Health System, National University of Singapore, 5 Lower Kent Ridge Road, 119074 Singapore
10 Stem Cells and Tissue Repair, Institute of Medical Biology, A*STAR, 8A Biomedical Grove, #06-06 Immunos, 138648 Singapore
Breast Cancer Research 2010, 12:R89 doi:10.1186/bcr2762
Published: 28 October 2010Abstract
Introduction
Metastatic breast cancer cells frequently and ectopically express the transcription factor RUNX2, which normally attenuates proliferation and promotes maturation of osteoblasts. RUNX2 expression is inversely regulated with respect to cell growth in osteoblasts and deregulated in osteosarcoma cells.
Methods
Here, we addressed whether the functional relationship between cell growth and RUNX2 gene expression is maintained in breast cancer cells. We also investigated whether the aberrant expression of RUNX2 is linked to phenotypic parameters that could provide a selective advantage to cells during breast cancer progression.
Results
We find that, similar to its regulation in osteoblasts, RUNX2 expression in MDA-MB-231 breast adenocarcinoma cells is enhanced upon growth factor deprivation, as well as upon deactivation of the mitogen-dependent MEK-Erk pathway or EGFR signaling. Reduction of RUNX2 levels by RNAi has only marginal effects on cell growth and expression of proliferation markers in MDA-MB-231 breast cancer cells. Thus, RUNX2 is not a critical regulator of cell proliferation in this cell type. However, siRNA depletion of RUNX2 in MDA-MB-231 cells reduces cell motility, while forced exogenous expression of RUNX2 in MCF7 cells increases cell motility.
Conclusions
Our results support the emerging concept that the osteogenic transcription factor RUNX2 functions as a metastasis-related oncoprotein in non-osseous cancer cells.