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J. Biol. Chem., Vol. 278, Issue 49, 48684-48689, December 5, 2003

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The Osteoblast Transcription Factor Runx2 Is Expressed in Mammary Epithelial Cells and Mediates osteopontin Expression^*

Claire K. Inman and Paul Shore

From the School of Biological Sciences, University of Manchester, 2.205, Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom

Targeted deletion of the Runx2 gene in mice has demonstrated that Runx2 is a master regulator of osteoblast differentiation. Runx2 has therefore largely been regarded as a bone-specific transcription factor. Runx2^–/– mice die shortly after birth and therefore the role of Runx2 in later developing tissues remains unclear. Here we show that the Runx2 protein is expressed in several mammary epithelial cell lines and in primary mammary epithelial cells. In addition, we have also found that it has a functionally important role in gene regulation. Osteopontin (OPN) is expressed in mammary epithelial cells during pregnancy and lactation and has been shown to have a role in mammary gland differentiation. Here we show that a Runx2 site in the OPN promoter is required for activation of the promoter in mammary epithelial cells. Moreover, dominant-negative Runx proteins can inhibit both activation of an OPN promoter reporter in transient transfections and expression of the endogenous OPN gene in mammary epithelial cells. Our data suggest, for the first time, that the osteoblast transcription factor Runx2 has a role in the normal regulation of gene expression in mammary epithelial cells.

Received for publication, July 23, 2003 , and in revised form, September 15, 2003.

^* This work was supported by a Wellcome Trust Career Development Fellowship (to P. S.) and a BBSRC studentship (to C. K. I). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 44-161-275-5978; Fax: 44-161-275-5082; E-mail: Paul.Shore{at}man.ac.uk.

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