Nature：一种新的肿瘤抑制基因

生物通报道，梅奥诊所实验病理学科，日本山梨大学医学院解剖与细胞生物学系，，美国南卡罗来纳医科大学儿童研究所，韦恩州立大学医学院放射肿瘤科等处的科学家发现一个名为TCEAL7的基因可能是一种新的肿瘤抑制基因。相关成果公布在Nature子刊Oncogene上。

　　

免费全文链接：http://www.nature.com/onc/journal/v27/n58/full/onc2008360a.html

 

原文摘要：A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc activity, cyclin D1 levels and cellular transformation

 

【Abstract】

The pathophysiological mechanisms that drive the development and progression of epithelial ovarian cancer remain obscure. Recently, we identified TCEAL7 as a transcriptional regulatory protein often downregulated in epithelial ovarian cancer. However, the biological significance of such downregulation in cancer is not currently known. Here, we show that TCEAL7 is downregulated frequently in many human cancers and that in immortalized human ovarian epithelial cells this event promotes anchorage-independent cell growth. Mechanistic investigations revealed that TCEAL7 associates with cyclin D1 promoter containing Myc E-box sequence and transcriptionally represses cyclin D1 expression. Moreover, downregulation of TCEAL7 promotes DNA-binding activity of Myc-Max, and upregulates the promoter activity of c-Myc-target gene, ornithine decarboxylase (ODC), whereas enhanced expression of TCEAL7 inhibits Myc-induced promoter activity of ODC. Our findings suggest that TCEAL7 may restrict ovarian epithelial cell transformation by limiting Myc activity. These results also suggest a potential, alternative mechanism by which c-Myc activity may be deregulated in cancer by the downregulation of TCEAL7.