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 language | English |
|---|---|
| Pages (from-to) | 10164-10169 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 95 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Aug 18 1998 |
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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 journal › Article
}
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.
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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 -