1. ¹Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
2. ²Institute for Protein Research, Osaka University, Osaka, Japan
3. ³Graduate School of Medicine, Osaka University, Osaka, Japan
4. ⁴Osaka National Hospital, Chuo, Osaka, Japan
5. ⁵Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari, Osaka, Japan

Correspondence: Dr M Yutsudo, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Osaka, Japan. E-mail: yutsudo@biken.osaka-u.ac.jp

Received 1 November 2005; Revised 18 April 2006; Accepted 5 May 2006; Published online 12 June 2006.

Abstract

Previously, we isolated a series of cell lines from a human diploid fibroblast lineage as a model for multistep tumorigenesis in humans. After passaging a single LT-transfected fibroblast clone, differently progressed cell lines were obtained, including immortalized, anchorage-independent and tumorigenic cell lines. In the present paper, we analysed the gene expression profiles of these model cell lines, and observed that expression of the CapG protein was lost in the tumorigenic cell line. To examine the possibility that loss of CapG protein expression was required for tumorigenic progression, we transfected CapG cDNA into the tumorigenic cell line and tested for tumor-forming ability in nude mice. Results showed that ectopic expression of CapG suppressed tumorigenicity, but not growth in soft agar or liquid medium. We also found that certain cancer cell lines including stomach cancer, lung cancer and melanoma had also lost CapG expression. One such cancer cell line AZ521 also became non-tumorigenic after the introduction of CapG cDNA. Moreover, we showed that CapG expression was repressed in small-cell lung cancer tissues. Together, our findings indicated that CapG is a new tumor suppressor gene involved in the tumorigenic progression of certain cancers.