A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals

Shinji Tanaka, Tsuyoshi Akiyoshi, Masaki Mori, Jack R. Wands, Keizo Sugimachi

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Abstract

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 β-catenin followed by nuclear translocation of β-catenin. Furthermore, cotransfection of a mutant construct encoding a FzE3 protein with a C-terminal truncation completely inhibited the interaction of APC with β-catenin in cells. Finally, coexpression of FzE3 with Lef-1 transcription factor enhanced β-catenin translocation to the nucleus. These observations suggest that FzE3 gene expression may down-regulate APC function and enhance β-catenin mediated signals in poorly differentiated human esophageal carcinomas.

Original languageEnglish
Pages (from-to)10164-10169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number17
DOIs
Publication statusPublished - Aug 18 1998

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All Science Journal Classification (ASJC) codes

  • General

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