UMMS Affiliation
Department of Cell Biology
Publication Date
2010-10-30
Document Type
Article
Subjects
Core Binding Factor Alpha 1 Subunit; Osteoblasts; Transcription Factors; Breast Neoplasms
Disciplines
Cell Biology
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.
Rights and Permissions
© 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.
DOI of Published Version
10.1186/bcr2762
Source
Breast Cancer Res. 2010 Oct 28;12(5):R89. Link to article on publisher's site.
Journal/Book/Conference Title
Breast cancer research : BCR
Related Resources
PubMed ID
21029421
Repository Citation
Leong, David T.; Pratap, 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.; and Voorhoeve, P. Mathijs, "Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility" (2010). Stein, Stein, Lian, vanWijnen Lab Publications. 1.
https://escholarship.umassmed.edu/stein/1