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.
