title: Regulation of extracellular matrix metalloproteinase inducer and matrix metalloproteinase expression by amphiregulin in transformed human breast epithelial cells.
abstract: 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.
authors: Laboratoire de Pharmacologie Experimentale et Clinique, Institut National de la Santé et de la Recherche Médicale INSERM E334, Institut de Génétique Moléculaire, Paris, France. s.menashi@chu-stlouis.fr
authors: Suzanne
authors: S
authors: Menashi
authors: Maria
authors: M
authors: Serova
authors: Lin
authors: L
authors: Ma
authors: Stephane
authors: S
authors: Vignot
authors: Samia
authors: S
authors: Mourah
authors: Fabien
authors: F
authors: Calvo
mesh_terms: D066258:Amphiregulin; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051926:Basigin; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000502:physiology; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D016373:DNA, Antisense / Q000235:genetics; D066255:EGF Family of Proteins; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D000077156:Gefitinib; D006023:Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C587849:Areg protein, mouse; C497886:BSG protein, human; C497887:Bsg protein, mouse; D016373:DNA, Antisense; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011799:Quinazolines; D012333:RNA, Messenger; D051926:Basigin; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077156:Gefitinib