1. ¹Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
2. ²Department Anesthesiology, Yokohama City University School of Medicine, Kanagawa, Japan
3. ³Promotion of Genome-based Medicine Project, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Correspondence: Dr Y Furukawa, Promotion of Genome-based Medicine Project, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. E-mail: furukawa@ims.u-tokyo.ac.jp

Received 6 December 2004; Revised 13 July 2005; Accepted 25 July 2005; Published online 19 September 2005.

Abstract

After analysing gene-expression profiles of colon cancers on a cDNA microarray containing cDNAs corresponding to 23 040 human genes, we focused on a gene annotated as C10orf3 (chromosome 10 open reading frame 3), whose expression was elevated in colorectal cancers (CRC) as well as in tumors arising in the stomach, lung, pancreas, and breast. The gene encodes a putative 464-amino-acid protein containing a domain known as AAA (ATPases associated with a variety of cellular activities). Western blot analysis using an antibody to the gene product confirmed that the protein was overexpressed in nine of the 15 clinical cancer tissues examined, compared to corresponding noncancerous epithelial cells. A subsequent proteomics analysis revealed that C10orf3 product associated with the product of tumor susceptibility gene 101 (TSG101), and that C10orf3 downregulated TSG101 in a post-transcriptional manner. Expression of short interfering RNA in cells derived from CRC caused significant decreases in C10orf3 expression and inhibited growth of the transfected cells, which was associated with increased apoptotic cells. These data suggest that elevated C10orf3 expression might play an essential role in the growth of cancer cells, and that suppression of C10orf3-mediated signal transduction may be a novel therapeutic strategy to a wide range of human tumors.