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Human Cancer Biology |
Authors' Affiliations: 1 Laboratory of Molecular Medicine; 2 Promotion of Genome-Based Medicine Project, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; and 3 Department of Gastroenterological Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Requests for reprints: Yoichi Furukawa, Promotion of Genome-Based Medicine Project, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639 Tokyo, Japan. Phone: 81-3-5449-5373; Fax: 81-3-5449-5124; E-mail: furukawa{at}ims.u-tokyo.ac.jp.
Purpose and Experimental Design: To discover novel therapeutic targets for colon cancers, we previously surveyed expression patterns among 23,000 genes in colon cancer tissues using a cDNA microarray. Among the genes that were up-regulated in the tumors, we selected for this study peptidyl-prolyl isomerase-like 1 (PPIL1) encoding PPIL1, a cyclophilin-related protein.
Results: Western blot analysis and immunohistochemical staining using PPIL1-specific antibody showed that PPIL1 protein was frequently overexpressed in colon cancer cells compared with noncancerous epithelial cells of the colon mucosa. Colony formation assay showed a growth-promoting effect of wild-type PPIL1 on NIH3T3 and HEK293 cells. Consistently, transfection of short-interfering RNA specific to PPIL1 into SNUC4 and SNUC5 cells effectively reduced expression of the gene and retarded growth of the colon cancer cells. We further identified two PPIL1-interacting proteins, SNW1/SKIP (SKI-binding protein) and stathmin. SNW1/SKIP is involved in the regulation of transcription and mRNA splicing, whereas stathmin is involved in stabilization of microtubules. Therefore, elevated expression of PPIL1 may play an important role in proliferation of cancer cells through the control of SNW1/SKIP and/or stathmin.
Conclusion: The findings reported here may offer new insight into colonic carcinogenesis and contribute to the development of new molecular strategies for treatment of human colorectal tumors.
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