PEA3 transactivates the Muc4/Sialomucin Complex promoter in mammary epithelial and tumor cells

doi:10.1074/jbc.M300264200

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Papers In Press, published online ahead of print July 10, 2003
J. Biol. Chem, 10.1074/jbc.M300264200
Submitted on January 9, 2003
Revised on June 18, 2003
Accepted on July 10, 2003

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

Cell Biology & Anatomy (R124), University of Miami School of Medicine, Miami, FL 33136

Corresponding Author: aperez6{at}med.miami.edu

Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein composed of two subunits, the mucin component ASGP-1 and the transmembrane subunit ASGP-2, which is aberrantly expressed on the surfaces of a variety of tumor cells. Upregulation of the Muc4/SMC gene in 13762 rat mammary adenocarcinoma cells 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 upregulation of Muc4/SMC transcription, whose gene product may contribute to the metastatic potential of mammary tumors.

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				V. Firlej, B. Bocquet, X. Desbiens, Y. de Launoit, and A. Chotteau-Lelievre Pea3 Transcription Factor Cooperates with USF-1 in Regulation of the Murine bax Transcription without Binding to an Ets-binding Site J. Biol. Chem., January 14, 2005; 280(2): 887 - 898. [Abstract] [Full Text] [PDF]

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