Regulation of extracellular matrix metalloproteinase inducer and matrix metalloproteinase expression by amphiregulin in transformed human breast epithelial cells.
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.
Menashi
Suzanne
S
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
Serova
Maria
M
Ma
Lin
L
Vignot
Stephane
S
Mourah
Samia
S
Calvo
Fabien
F
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
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