The SYT-SSX Fusion Protein Down-Regulates the Cell Proliferation Regulator COM1 in t(x;18) Synovial Sarcoma
-
Published:2007-02-15
Issue:4
Volume:27
Page:1348-1355
-
ISSN:0270-7306
-
Container-title:Molecular and Cellular Biology
-
language:en
-
Short-container-title:Mol Cell Biol
Author:
Ishida Michiko1, Miyamoto Mamiko12, Naitoh Sayu12, Tatsuda Daisuke1, Hasegawa Tadashi3, Nemoto Takeshi14, Yokozeki Hiroo4, Nishioka Kiyoshi4, Matsukage Akio2, Ohki Misao1, Ohta Tsutomu1
Affiliation:
1. Center for Medical Genomics 2. Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo, Japan 3. Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan 4. Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Abstract
ABSTRACT
Chromosomal translocations are frequently associated with soft-tissue sarcomas. Fusion proteins generated by such translocations often play critical roles in tumorigenesis. Therefore, it is important to understand the function of the fusion protein to develop therapeutic interventions. The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in a fusion between the SYT gene on chromosome 18 and an SSX gene on the X chromosome. Although SYT-SSX fusion proteins appear to trigger synovial sarcoma development, little is known about the downstream targets of SYT-SSX. We found that the SYT-SSX fusion protein produces a dominant-negative function for SYT, which is a transcriptional coactivator. We then analyzed the gene expression profiles of SYT-SSX1-expressing HeLa cells using oligonucleotide microarrays and found that the SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. COM1 was found to be expressed at relatively low levels in synovial sarcoma tissues and cell lines. We then investigated the impact of conditional COM1 expression in the synovial sarcoma cell line. Increased COM1 expression resulted in induced apoptosis and in reduced cell growth and colony formation activity. Our results suggested that restoration of COM1 expression may be of therapeutic benefit in synovial sarcoma.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference33 articles.
1. Bedner, E., P. Smolewski, P. Amstad, and Z. Darzynkiewicz. 2000. Activation of caspases measured in situ by binding of fluorochrome-labeled inhibitors of caspases (FLICA): correlation with DNA fragmentation. Exp. Cell Res.259:308-313. 2. Bratland, A., K. Risberg, G. M. Maelandsmo, K. B. Gutzkow, O. E. Olsen, A. Moghaddam, M. Y. Wang, C. M. Hansen, H. K. Blomhoff, J. P. Berg, O. Fodstad, and A. H. Ree. 2000. Expression of a novel factor, com1, is regulated by 1,25-dihydroxyvitamin D3 in breast cancer cells. Cancer Res.60:5578-5583. 3. Brett, D., S. Whitehouse, P. Antonson, J. Shipley, C. Cooper, and G. Goodwin. 1997. The SYT protein involved in the t(X;18) synovail sarcoma translocation is a transcriptional activator localised in nuclear bodies. Hum. Mol. Genet.6:1559-1564. 4. Carracedo, A., M. Lorente, A. Egia, C. Blazquez, S. Garcia, V. Giroux, C. Malicet, R. Villuendas, M. Gironella, L. Gonzalez-Feria, M. A. Piris, J. L. Iovanna, M. Guzman, and G. Velasco. 2006. The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell4:301-312. 5. Clark, J., P. J. Rocques, A. J. Crew, S. Gill, J. Shipley, A. M. Chan, B. A. Gusterson, and C. S. Cooper. 1994. Identification of novel genes, SYT and SSX, in the t(X;19)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat. Genet.7:502-508.
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|