Watari A, Takaki K, Higashiyama S, Li Y, Satomi Y, Takao T, Tanemura A, Yamaguchi Y, Katayama I, Shimakage M, Miyashiro I, Takami K, Kodama K, Yutsudo M
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Oncogene. 2006 Nov 30;25(56):7373-80. doi: 10.1038/sj.onc.1209732. Epub 2006 Jun 12.
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.
此前，我们从人类二倍体成纤维细胞系中分离出一系列细胞系，作为人类多步骤肿瘤发生的模型。在传代单个LT转染的成纤维细胞克隆后，获得了不同进展阶段的细胞系，包括永生化、不依赖贴壁和致瘤性细胞系。在本文中，我们分析了这些模型细胞系的基因表达谱，观察到致瘤性细胞系中CapG蛋白的表达缺失。为了研究CapG蛋白表达缺失是否是致瘤进展所必需的，我们将CapG cDNA转染到致瘤性细胞系中，并在裸鼠中测试其形成肿瘤的能力。结果表明，CapG的异位表达抑制了致瘤性，但不影响在软琼脂或液体培养基中的生长。我们还发现，包括胃癌、肺癌和黑色素瘤在内的某些癌细胞系也失去了CapG表达。其中一个癌细胞系AZ521在导入CapG cDNA后也变得不再具有致瘤性。此外，我们表明CapG表达在小细胞肺癌组织中受到抑制。总之，我们的研究结果表明CapG是一种新的肿瘤抑制基因，参与某些癌症的致瘤进展。
