Colorectal Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 14, 2006; 12(10): 1529-1535
Published online Mar 14, 2006. doi: 10.3748/wjg.v12.i10.1529
Reduced expression of β-catenin inhibitor Chibby in colon carcinoma cell lines
Marion M Schuierer, Elisabeth Graf, Ken-Ichi Takemaru, Wolfgang Dietmaier, Anja-Katrin Bosserhoff
Marion M Schuierer, Elisabeth Graf, Wolfgang Dietmaier, Anja-Katrin Bosserhoff, Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
Ken-Ichi Takemaru, Department of Pharmacology, BST 7-168, Stony Brook, NY 11794-8651, United States
Author contributions: All authors contributed equally to the work.
Supported by grants from the DFG and the Deutsche Krebshilfe to A.B.
Correspondence to: Anja Bosserhoff, PhD, University of Regensburg, Institute of Pathology, Franz-Josef-Straus-Allee 11, 93053 Regensburg, Germany.
Telephone: +49-941-9446705 Fax: +49-941-9446602
Received: July 5, 2005
Revised: September 12, 2005
Accepted: November 18, 2005
Published online: March 14, 2006

AIM: To analyse the Chibby expression and its function in colon carcinoma cell lines and colorectal carcinoma (CRC).

METHODS: Chibby expression levels were investigated by quantitative RT-PCR in a panel of seven different colon carcinoma cell lines. By sequencing, we analysed mutational status of Chibby. To test whether Chibby exhibited effects on β-catenin signalling in colon carcinoma cells, we transfected SW480 cells with Chibby expression plasmid and, subsequently, analysed activity of β-catenin and tested for alterations in cellular phenotype. In addition, we examined Chibby mRNA levels in samples of colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR and hybridised gene chips with samples from CRC and normal tissues.

RESULTS: Chibby mRNA expression was strongly down-regulated in colon carcinoma cell lines in comparison to normal colon epithelial cells and no mutation in any of the examined colon carcinoma cell lines was found. Further, we could show that Chibby inhibited β-catenin activity in TOPflash assays when over-expressed in SW480 cells. Proliferation and invasion assays with Chibby transfected SW480 cells did not reveal profound differences compared to control cells. In contrast to these in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor samples did not show significant differences to specimens in adjacent non-cancerous tissue. Consistent with these findings, gene chips analysing tissue samples of tumors and corresponding normal tissue did not show altered Chibby expression

CONCLUSION: Altered Chibby expression might be observed in vitro in different colon carcinoma cell lines. However, this finding could not be confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote CRC tumor development or progression. As Chibby is an important inhibitor of ß-catenin signalling, our data implicate that the usability of colon carcinoma cell lines for in vitro studies analysing the Wnt/β-catenin pathway in colorectal carcinoma needs extensive verification.

Keywords: Chibby, Wnt, β-catenin, Colorectal carcinoma, Colon carcinoma cell lines