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[Cancer Research 63, 7575-7580, November 15, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Regulation of Extracellular Matrix Metalloproteinase Inducer and Matrix Metalloproteinase Expression by Amphiregulin in Transformed Human Breast Epithelial Cells

Suzanne Menashi2, Maria Serova1, Lin Ma3, Stephane Vignot1, Samia Mourah1 and Fabien Calvo1

1 Laboratoire de Pharmacologie Experimentale et Clinique, Institut National de la Santé et de la Recherche Médicale INSERM E334, Institut de Génétique Moléculaire, Paris, France;
2 Institut National de la Santé et de la Recherche Médicale INSERM U532, Hôpital Saint-Louis, Paris, France;
3 Department of Radiotherapy, Chinese PLA General Hospital, Beijing, China

Amphiregulin (AR) and epidermal growth factor effects on expression and activity of the extracellular matrix metalloproteinase inducer (EMMPRIN) were examined in NS2T2A1 breast tumor cells. Both growth factors induced mRNA and protein expression of EMMPRIN, and matrix metalloproteinase (MMP) -2 and -9 enzymatic activity. The induction of EMMPRIN by AR was mediated by epidermal growth factor receptor (EGFR) tyrosine kinase activation and inhibited by ZD1839. AR and EGFR antisense (AS) cDNAs inhibited EMMPRIN expression and MMP activity. Coculture of NS2T2A1V expressing AR- or EGFR-AS with fibroblasts and endothelial cells showed a decreased MMP activity. In parallel, nude mice tumors derived from AR and EGFR-AS cells revealed reduced level of EMMPRIN and MMP activity. AR and epidermal growth factor, therefore, regulate EMMPRIN and its MMP-mediated expression, identifying EGFR signaling as critical to this regulation.




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