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J. Biol. Chem., Vol. 278, Issue 38, 36942-36952, September 19, 2003

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PEA3 Transactivates the Muc4/Sialomucin Complex Promoter in Mammary Epithelial and Tumor Cells^*

Aymee Perez , Roy Barco , Isabel Fernandez, Shari A. Price-Schiavi ¶ and Kermit L. Carraway

From the Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101

Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein composed of two subunits, the mucin component ascites sialoglycoprotein ASGP-1 and the transmembrane subunit ASGP-2, which is aberrantly expressed on the surfaces of a variety of tumor cells. Up-regulation of the Muc4/SMC gene in the 13762 sublines of the rat mammary adenocarcinoma correlates with the overexpression of transcription factor PEA3 and the receptor tyrosine kinase ErbB2. Here we report that PEA3 is capable of transactivating the Muc4/SMC promoter in a dose-dependent manner via direct attachment to a PEA3 binding site. ERM and ER81, the other two members of the PEA3 subfamily of transcription factors, could not transactivate the Muc4/SMC promoter. Transcriptional activation of Muc4/SMC by PEA3 is potentiated by Ras and MEKK1 kinases. These data suggest that expression of PEA3 in mammary tumors leads to up-regulation of Muc4/SMC transcription, the gene product of which may contribute to the metastatic potential of mammary tumors.

Received for publication, January 9, 2003 , and in revised form, June 18, 2003.

^* This work was supported in part by Grants CA-84178 (to A. P.) and CA52498 (to K. L. C.) from the National Institutes of Health and the Sylvester Comprehensive Cancer Center of the University of Miami. 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.

Present address: Vanderbilt University School of Medicine, Nashville, TN 37232.

^¶ Present address: Sunol Molecular Corp., Miramar, FL 33025.

To whom correspondence should be addressed: Dept. of Cell Biology (R-124), University of Miami School of Medicine, P. O. Box 016960, Miami, FL 33101. E-mail: aperez6{at}med.miami.edu.

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