PEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells.
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.
Perez
Aymee
A
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA. aperez6@med.miami.edu
Barco
Roy
R
Fernandez
Isabel
I
Price-Schiavi
Shari A
SA
Carraway
Kermit L
KL
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008957:Models, Genetic; D055264:Mucin-4; D009077:Mucins / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism
D005982:Glutathione Transferase; D008156:Luciferases; D055264:Mucin-4; D009077:Mucins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D018631:ras Proteins; C524660:Muc4 protein, rat; C065788:transcription factor PEA3