Transcriptional regulation of subtilisin-like proprotein convertase PACE4 by E2F: Possible role of E2F-mediated upregulation of PACE4 in tumor progression
作者： Keizo Yuasa , Kaori Suzue , Masami Nagahama , Yoshiko Matsuda , Akihiko Tsuji
DOI: 10.1016/J.GENE.2007.07.028
关键词:
摘要: PACE4, a member of the subtilisin-like proprotein convertase (SPC) family, is expressed at high levels in certain tumor cells and plays role metastatic progression through activation matrix metalloproteinases. The mechanism leading to overexpression PACE4 remains unclear. In this study, we show that E2F1 transcription factor, which implicated carcinoma invasiveness, upregulates expression PACE4. HT1080 (highly tumorigenic invasive) much higher E2F family (E2F1 E2F2) transcripts than IMR90 (normal fibroblast) cells. Expression other SPCs (furin PC6) remained unchanged these Promoter analysis indicated two consensus binding sites (-117/-110 -86/-79) 5'-flanking region human gene function as positive regulatory elements. Mutation abolished promoter response well electrophoretic mobility-shift assays. Other members, E2F2 E2F3, also activated expression, case E2F1. These results indicate novel for family-mediated promotion invasiveness
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