Abstract
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.
Highlights
Muc4/SMC1 is a membrane mucin isolated from the highly metastatic 13762 ascites sublines of a rat mammary adenocarcinoma [1]
Because PEA3 is a key regulator of ErbB2 overexpression in human and mouse breast tumors [37, 38], we decided to explore the link among Muc4/SMC, ErbB2, and PEA3 in 13762 rat mammary adenocarcinoma sublines and normal mammary epithelial cells
To compare the level of Muc4/SMC, ErbB2, and PEA3 expression in the rat tumor cells to that in normal mammary epithelial cells, cells from three different sublines of the 13762 rat mammary adenocarcinoma and normal mammary tissue were solubilized in 1% SDS, and total protein was quantified by BCA assay
Summary
Muc4/SMC1 is a membrane mucin isolated from the highly metastatic 13762 ascites sublines of a rat mammary adenocarcinoma [1]. MUC4/SMC, ErbB2, and PEA3 Are Up-regulated in 13762 Tumor Cells Compared with Normal Mammary Epithelial Cells—Muc4/SMC was originally isolated from highly proliferative and metastatic ascites sublines of the 13762 rat mammary adenocarcinoma [12].
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