Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer

We investigated whether one of the Wnt receptors, frizzled-7 (FZD7), functions in the canonical Wnt signaling pathway of colorectal cancer (CRC) cells harboring an APC or CTNNB1 mutation and may be a potential therapeutic target for sporadic CRCs. The expression level of FZD gene family members in...

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Main Authors: Koji Ueno, Mikako Hiura, Yutaka Suehiro, Shoichi Hazama, Hiroshi Hirata, Masaaki Oka, Kohzoh Imai, Rajvir Dahiya, Yuji Hinoda
Format: Article
Language:English
Published: Elsevier 2008-07-01
Series:Neoplasia: An International Journal for Oncology Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558608800085
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spelling doaj-542ac7ff24614c96941d9812f20bfcdd2020-11-25T01:08:16ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-07-0110769770510.1593/neo.08320Frizzled-7 as a Potential Therapeutic Target in Colorectal CancerKoji Ueno0Mikako Hiura1Yutaka Suehiro2Shoichi Hazama3Hiroshi Hirata4Masaaki Oka5Kohzoh Imai6Rajvir Dahiya7Yuji Hinoda8Department of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, JapanDepartment of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, JapanDepartment of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, JapanDepartment of Surgery II, Yamaguchi University Graduate School of Medicine, Ube, JapanDepartment of Urology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA, USADepartment of Surgery II, Yamaguchi University Graduate School of Medicine, Ube, JapanSapporo Medical University, Sapporo, JapanDepartment of Urology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA, USADepartment of Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan We investigated whether one of the Wnt receptors, frizzled-7 (FZD7), functions in the canonical Wnt signaling pathway of colorectal cancer (CRC) cells harboring an APC or CTNNB1 mutation and may be a potential therapeutic target for sporadic CRCs. The expression level of FZD gene family members in colon cancer cells and primary CRC tissues were determined by real-time PCR. Activation of the Wnt signaling pathway was evaluated by TOPflash assay. The expression level of Wnt target genes was determined by real-time polymerase chain reaction and/or Western blot analysis. Cell growth and cell invasion were assessed by MTS and matrigel assays, respectively. Among 10 FZD gene family members, FZD7 mRNA was predominantly expressed in six colon cancer cell lines with APC or CTNNB1 mutation. These six cell lines were transfected with FZD7 cDNA together with a TOPflash reporter plasmid, resulting in a 1.5- to 24.3-fold increase of Tcf transcriptional activity. The mRNA expression levels of seven known Wnt target genes were also increased by 1.5- to 3.4-fold after transfection of FZD7 cDNA into HCT-116 cells. The six cell lines were then cotransfected with FZD7-siRNA and a TOPflash reporter plasmid, which reduced Tcf transcriptional activity to 20% to 80%. FZD7-siRNA was shown to significantly decrease cell viability and in vitro invasion activity after transfection into HCT-116 cells. Our present data demonstrated that FZD7 activates the canonical Wnt pathway in colon cancer cells despite the presence of APC or CTNNB1 mutation and that FZD7-siRNA may be used as a therapeutic reagent for CRCs. http://www.sciencedirect.com/science/article/pii/S1476558608800085
collection DOAJ
language English
format Article
sources DOAJ
author Koji Ueno
Mikako Hiura
Yutaka Suehiro
Shoichi Hazama
Hiroshi Hirata
Masaaki Oka
Kohzoh Imai
Rajvir Dahiya
Yuji Hinoda
spellingShingle Koji Ueno
Mikako Hiura
Yutaka Suehiro
Shoichi Hazama
Hiroshi Hirata
Masaaki Oka
Kohzoh Imai
Rajvir Dahiya
Yuji Hinoda
Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer
Neoplasia: An International Journal for Oncology Research
author_facet Koji Ueno
Mikako Hiura
Yutaka Suehiro
Shoichi Hazama
Hiroshi Hirata
Masaaki Oka
Kohzoh Imai
Rajvir Dahiya
Yuji Hinoda
author_sort Koji Ueno
title Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer
title_short Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer
title_full Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer
title_fullStr Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer
title_full_unstemmed Frizzled-7 as a Potential Therapeutic Target in Colorectal Cancer
title_sort frizzled-7 as a potential therapeutic target in colorectal cancer
publisher Elsevier
series Neoplasia: An International Journal for Oncology Research
issn 1476-5586
1522-8002
publishDate 2008-07-01
description We investigated whether one of the Wnt receptors, frizzled-7 (FZD7), functions in the canonical Wnt signaling pathway of colorectal cancer (CRC) cells harboring an APC or CTNNB1 mutation and may be a potential therapeutic target for sporadic CRCs. The expression level of FZD gene family members in colon cancer cells and primary CRC tissues were determined by real-time PCR. Activation of the Wnt signaling pathway was evaluated by TOPflash assay. The expression level of Wnt target genes was determined by real-time polymerase chain reaction and/or Western blot analysis. Cell growth and cell invasion were assessed by MTS and matrigel assays, respectively. Among 10 FZD gene family members, FZD7 mRNA was predominantly expressed in six colon cancer cell lines with APC or CTNNB1 mutation. These six cell lines were transfected with FZD7 cDNA together with a TOPflash reporter plasmid, resulting in a 1.5- to 24.3-fold increase of Tcf transcriptional activity. The mRNA expression levels of seven known Wnt target genes were also increased by 1.5- to 3.4-fold after transfection of FZD7 cDNA into HCT-116 cells. The six cell lines were then cotransfected with FZD7-siRNA and a TOPflash reporter plasmid, which reduced Tcf transcriptional activity to 20% to 80%. FZD7-siRNA was shown to significantly decrease cell viability and in vitro invasion activity after transfection into HCT-116 cells. Our present data demonstrated that FZD7 activates the canonical Wnt pathway in colon cancer cells despite the presence of APC or CTNNB1 mutation and that FZD7-siRNA may be used as a therapeutic reagent for CRCs.
url http://www.sciencedirect.com/science/article/pii/S1476558608800085
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