A novel amplification target, ARHGAP5, promotes cell spreading and migration by negatively regulating RhoA in Huh-7 hepatocellular carcinoma cells

Gen, Yasuyuki; Yasui, Kohichiroh; Zen, Keika; Nakajima, Tomoaki; Tsuji, Kazuhiro; Endo, Mio; Mitsuyoshi, Hironori; Minami, Masahito; Itoh, Yoshito; Tanaka, Shinji; Taniwaki, Masafumi; Arii, Shigeki; Okanoue, Takeshi; Yoshikawa, Toshikazu

doi:10.1016/j.canlet.2008.09.036

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Volume 275, Issue 1 , Pages 27-34, 8 March 2009

A novel amplification target, ARHGAP5, promotes cell spreading and migration by negatively regulating RhoA in Huh-7 hepatocellular carcinoma cells

Yasuyuki Gen
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Kohichiroh Yasui
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
- Corresponding author. Tel.: +81 75 251 5519; fax: +81 75 251 0710.
Keika Zen
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Tomoaki Nakajima
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Kazuhiro Tsuji
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Mio Endo
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Hironori Mitsuyoshi
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Masahito Minami
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Yoshito Itoh
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Shinji Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Masafumi Taniwaki
- Molecular Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Shigeki Arii
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Takeshi Okanoue
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
- Department of Hepatology, Saiseikai Suita Hospital, Suita, Osaka 564-0013, Japan
Toshikazu Yoshikawa
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan

Received 19 August 2008; received in revised form 23 September 2008; accepted 30 September 2008. published online 10 November 2008.

Abstract

RhoA, a member of the Rho family of small GTPases, directs the organization of the actin cytoskeleton and is involved in regulating cell shape and movement. Its activity is negatively regulated by p190-B RhoGAP (GTPase-activating protein). We investigated DNA copy number aberrations in human hepatocellular carcinoma and esophageal squamous cell carcinoma cell lines using a high-density oligonucleotide microarray and found a novel amplification at chromosomal region 14q12. We identified ARHGAP5 (the gene encoding p190-B RhoGAP) as a probable target for the amplification at 14q12, and our results showed that p190-B RhoGAP promotes cells spreading and migration by negatively regulating RhoA activity in Huh-7 hepatocellular carcinoma cells.

Keywords: ARHGAP5, p190-B RhoGAP, RhoA, Amplification, Hepatocellular carcinoma