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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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.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558608800085 |
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