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World J Gastroenterol. May 21, 2007; 13(19): 2717-2721
Published online May 21, 2007. doi: 10.3748/wjg.v13.i19.2717
TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is up-regulated in colon carcinoma and involved in cell proliferation and cell aggregation
Yuji Toiyama, Akira Mizoguchi, Kazushi Kimura, Junichirou Hiro, Yasuhiro Inoue, Tomonari Tutumi, Chikao Miki, Masato Kusunoki
Yuji Toiyama, Junichirou Hiro, Yasuhiro Inoue, Chikao Miki, Masato Kusunoki, Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Japan
Akira Mizoguchi, Kazushi Kimura, Tomonari Tutumi, Department of Anatomy, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu Mie 514-8507, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Masato Kusunoki, MD, Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. kusunoki@clin.medic.mie-u.ac.jp
Telephone: +81-59-2315294 Fax: +81-59-2326968
Received: February 5, 2007
Revised: February 20, 2007
Accepted: March 1, 2007
Published online: May 21, 2007
Abstract

AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon cancer cell lines.

METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.

RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P = 0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 significantly inhibited both proliferation and scattering of these cancer cell lines.

CONCLUSION: The present work demonstrates, for the first time, that the TTYH2 gene expression is significantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating and metastatic potentials of colorectal cancer.

Keywords: TTYH2, Colorectal carcinoma, Cell proliferation, Cell aggregation