口腔癌細胞における新規低酸素誘導遺伝子EFEMP2機能解析

点击翻译按钮获取中文摘要

Tumor hypoxia alters expression of various genes via hypoxia-inducible transcription factors, resulting causes numerous changes linked to the biologically aggressive phenotype. We identified EFEMP2 as a novel hypoxia-inducible gene by using oligonucleotide array, and demonstrated that the gene could decrease p53 activity in cancer cells. The expression levels of EFEMP2 were significantly higher in both colon and esophageal cancers compared to the adjacent normal tissues. Promoter reporters showed significant activities in several cancer cells and the activities were increased under hypoxic conditions (1% pO_2) or by cotransfection of HIF-1α. Forced expression of EFEMP2 decreased p53 protein levels and its activity in cancer cells, and also attenuated Notch signaling. Taken together, we demonstrated that EFEMP2 was transcriptionally induced by HIF-1 and its protein regulated cancer cell proliferation via p53 regulations.