Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility
Authors
Leong, David TPratap, Jitesh
Pereira, Barry P.
Nathan, Saminathan S.
Dobson, Jason R.
Lian, Jane B.
Ito, Yoshiaki
Stein, Gary S.
Salto-Tellez, Manuel
Cool, Simon M.
Van Wijnen, Andre J.
Lim, Joleen
Goh, Xuewei
Kwok, Hui S.
Voorhoeve, P. Mathijs
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2010-10-30Keywords
Core Binding Factor Alpha 1 SubunitOsteoblasts
Transcription Factors
Breast Neoplasms
Cell Biology
Metadata
Show full item recordAbstract
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.Source
Breast Cancer Res. 2010 Oct 28;12(5):R89. Link to article on publisher's site.DOI
10.1186/bcr2762Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49445PubMed ID
21029421Related Resources
Link to Article in PubMedRights
© 2010 Leong et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.ae974a485f413a2113503eed53cd6c53
10.1186/bcr2762