1. ¹Department of Pathology, School of Medicine, Keio University, Tokyo, Japan
2. ²Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
3. ³Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
4. ⁴Cancer Genomics Division, National Cancer Center Research Institute, Tokyo, Japan
5. ⁵Pathology Division, National Cancer Center Research Institute, Tokyo, Japan

Correspondence: Professor M Sakamoto, MD, PhD, Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: msakamot@sc.itc.keio.ac.jp

Received 19 September 2008; Revised 5 December 2008; Accepted 9 December 2008; Published online 2 February 2009.

Abstract

Pancreatic cancer has the worst prognosis among cancers due to the difficulty of early diagnosis and its aggressive behavior. To characterize the aggressiveness of pancreatic cancers on gene expression, pancreatic cancer xenografts transplanted into severe combined immunodeficient mice served as a panel for gene-expression profiling. As a result of profiling, the adenylate cyclase-associated protein 1 (CAP1) gene was shown to be overexpressed in all of the xenografts. The expression of CAP1 protein in all 73 cases of pancreatic cancer was recognized by immunohistochemical analyses. The ratio of CAP1-positive tumor cells in clinical specimens was correlated with the presence of lymph node metastasis and neural invasion, and also with the poor prognosis of patients. Immunocytochemical analyses in pancreatic cancer cells demonstrated that CAP1 colocalized to the leading edge of lamellipodia with actin. Knockdown of CAP1 by RNA interference resulted in the reduction of lamellipodium formation, motility, and invasion of pancreatic cancer cells. This is the first report demonstrating the overexpression of CAP1 in pancreatic cancers and suggesting the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells.