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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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

Fingerprint

Catenins
Adenomatous Polyposis Coli
Carcinoma
Genes
Complementary DNA
Sequence Homology
Transfection
Cysteine
Mucous Membrane
Proteins
Transcription Factors
Down-Regulation
Ligands
Gene Expression
Amino Acids

All Science Journal Classification (ASJC) codes

  • General

Cite this

A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals. / Tanaka, Shinji; Akiyoshi, Tsuyoshi; Mori, Masaki; Wands, Jack R.; Sugimachi, Keizo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 17, 18.08.1998, p. 10164-10169.

Research output: Contribution to journalArticle

@article{e5148c1dbe1c4d93bf12b3abfc8e304c,
title = "A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals",
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.",
author = "Shinji Tanaka and Tsuyoshi Akiyoshi and Masaki Mori and Wands, {Jack R.} and Keizo Sugimachi",
year = "1998",
month = "8",
day = "18",
doi = "10.1073/pnas.95.17.10164",
language = "English",
volume = "95",
pages = "10164--10169",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "17",

}

TY - JOUR

T1 - A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals

AU - Tanaka, Shinji

AU - Akiyoshi, Tsuyoshi

AU - Mori, Masaki

AU - Wands, Jack R.

AU - Sugimachi, Keizo

PY - 1998/8/18

Y1 - 1998/8/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032544039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032544039&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.17.10164

DO - 10.1073/pnas.95.17.10164

M3 - Article

C2 - 9707618

AN - SCOPUS:0032544039

VL - 95

SP - 10164

EP - 10169

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -