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(American Journal of Pathology. 2004;164:987-995.)
© 2004 American Society for Investigative Pathology

ARK5 Expression in Colorectal Cancer and Its Implications for Tumor Progression

Gen-ichi Kusakai^*, Atsushi Suzuki^*, Tsutomu Ogura^*, Sin’ichi Miyamoto, Atsushi Ochiai, Michio Kaminishi and Hiroyasu Esumi^*

From the Investigative Treatment Division,^* and Pathology Division, National Cancer Center, Research Institute East, Kashiwa, Chiba; and the Department of Gastrointestinal Surgery, University of Tokyo, Bunkyo-ku, Tokyo, Japan

A novel member of the human AMPK family, ARK5, was recently discovered to be a key molecule in mediating cancer cell migration activity in human pancreas cancer cell line PANC-1, and its activation was found to be induced by Akt-dependent phosphorylation at Ser 600. DNA array analysis with 241 paired cDNAs from 13 different types of tumors and corresponding normal tissues derived from cancer patients revealed ARK5 overexpression in the samples of colorectal cancer. ARK5 expression was measured and an in vitro invasion assay was performed in six human colorectal cancer cell lines, WiDr, HCT-15, DLD-1, SW620, LoVo, and SW480, and since high invasion activity was concordant with higher ARK5 expression, ARK5 expression was examined in relation to tumor progression and metastatic activity in clinical samples. In 56 clinical samples of primary colorectal cancers and their liver metastases, higher ARK5 expression was observed in the samples from more advanced cases, and much higher expression was observed in the liver metastases. In situ hybridization analysis showed ARK5 overexpression in tumor cells. Based on these findings, we propose that ARK5 overexpression is involved in tumor progression of colon cancer clinically.

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