Menashi Suzanne, Serova Maria, Ma Lin, Vignot Stephane, Mourah Samia, Calvo Fabien
Laboratoire de Pharmacologie Experimentale et Clinique, Institut National de la Santé et de la Recherche Médicale INSERM E334, Institut de Génétique Moléculaire, Paris, France.
Cancer Res. 2003 Nov 15;63(22):7575-80.
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.
在NS2T2A1乳腺肿瘤细胞中检测了双调蛋白（AR）和表皮生长因子对细胞外基质金属蛋白酶诱导剂（EMMPRIN）表达及活性的影响。两种生长因子均诱导了EMMPRIN的mRNA和蛋白表达，以及基质金属蛋白酶（MMP）-2和-9的酶活性。AR对EMMPRIN的诱导作用由表皮生长因子受体（EGFR）酪氨酸激酶激活介导，并被ZD1839抑制。AR和EGFR反义（AS）cDNA抑制了EMMPRIN表达和MMP活性。将表达AR-或EGFR-AS的NS2T2A1V与成纤维细胞和内皮细胞共培养，显示MMP活性降低。同时，源自AR和EGFR-AS细胞的裸鼠肿瘤显示EMMPRIN水平和MMP活性降低。因此，AR和表皮生长因子调节EMMPRIN及其MMP介导的表达，表明EGFR信号传导对该调节至关重要。
