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01.10.2010 | Research article | Ausgabe 5/2010 Open Access

Breast Cancer Research 5/2010

Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility

Zeitschrift:
Breast Cancer Research > Ausgabe 5/2010
Autoren:
David T Leong, Joleen Lim, Xuewei Goh, Jitesh Pratap, Barry P Pereira, Hui Si Kwok, Saminathan Suresh Nathan, Jason R Dobson, Jane B Lian, Yoshiaki Ito, P Mathijs Voorhoeve, Gary S Stein, Manuel Salto-Tellez, Simon M Cool, Andre J van Wijnen
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​bcr2762) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

DTL, GSS, MST, SMC and AJVW made substantial contributions to the conception, design and analysis of the experiments, to the interpretation of data, as well as to drafting and revising the manuscript. SSN, JBL, YI and PMV made substantial contributions to the interpretation of data, as well as to revising the manuscript. JL, XG, JP, BPP and HSK designed and executed experiments, as well as assisted in the drafting of the manuscript. All authors read and approved the final manuscript.

Abstract

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.
Zusatzmaterial
Authors’ original file for figure 1
13058_2010_2744_MOESM1_ESM.pdf
Authors’ original file for figure 2
13058_2010_2744_MOESM2_ESM.pdf
Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
13058_2010_2744_MOESM5_ESM.pdf
Literatur
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