Cancer Research AACR Conference on Molecular Diagnostics - 2008 AACR Conference on Molecular Diagnostics - 2008
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[Cancer Research 63, 6116-6120, October 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Involvement of the FGF18 Gene in Colorectal Carcinogenesis, as a Novel Downstream Target of the ß-Catenin/T-Cell Factor Complex1

Takashi Shimokawa, Yoichi Furukawa, Michihiro Sakai, Meihua Li, Nobutomo Miwa, Yu-Min Lin and Yusuke Nakamura2

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

To search for potential molecular targets for development of novel anticancer drugs, we have been analyzing expression profiles of clinical samples from cancer patients, using a genome-wide cDNA microarray. In experiments with colon cancer cells, the gene encoding fibroblast growth factor 18 (FGF18) was among those that showed elevated expression. The promoter region of this gene was found to contain putative Tcf4-binding motifs; moreover a reporter-gene assay using luciferase activity as a marker and an electromobility shift assay indicated that FGF18 is a downstream transcription target in the ß-catenin/Tcf4 pathway. We showed that exogenous FGF18 promoted growth of NIH3T3 cells in an autocrine manner and that transfection of FGF18 short interfering RNAs suppressed growth of colon cancer cells in culture. Our results indicate that FGF18 is activated in colon cancers as a direct downstream target of the Wnt signaling pathway and that it might represent a marker for early diagnosis and a molecular target for treatment of this life-threatening tumor.




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