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  • 标题:A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals
  • 本地全文:下载
  • 作者:Shinji Tanaka ; Tsuyoshi Akiyoshi ; Masaki Mori
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1998
  • 卷号:95
  • 期号:17
  • 页码:10164-10169
  • DOI:10.1073/pnas.95.17.10164
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:A novel member of the human frizzled (Fz) gene family was cloned and found to be specifically expressed in 3 of 13 well differentiated (23%), 13 of 20 moderately differentiated (62%), and 12 of 14 poorly differentiated (86%) squamous cell esophageal carcinomas compared with the adjacent uninvolved normal mucosa. The FzE3 cDNA encodes a protein of 574 amino acids and shares high sequence homology with the human FzD2 gene particularly in the putative ligand binding region of the cysteine-rich extracellular domain. Functional analysis revealed that transfection and expression of the FzE3 cDNA in esophageal carcinoma cells stimulates complex formation between adenomatous polyposis coli (APC) and {beta}-catenin followed by nuclear translocation of {beta}-catenin. Furthermore, cotransfection of a mutant construct encoding a FzE3 protein with a C-terminal truncation completely inhibited the interaction of APC with {beta}-catenin in cells. Finally, coexpression of FzE3 with Lef-1 transcription factor enhanced {beta}-catenin translocation to the nucleus. These observations suggest that FzE3 gene expression may down-regulate APC function and enhance {beta}-catenin mediated signals in poorly differentiated human esophageal carcinomas.
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