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Molecular and Cellular Biology, February 2007, p. 1348-1355, Vol. 27, No. 4
0270-7306/07/$08.00+0     doi:10.1128/MCB.00658-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The SYT-SSX Fusion Protein Down-Regulates the Cell Proliferation Regulator COM1 in t(x;18) Synovial Sarcoma{triangledown} ,{dagger}

Michiko Ishida,1,{ddagger} Mamiko Miyamoto,1,2,{ddagger} Sayu Naitoh,1,2 Daisuke Tatsuda,1 Tadashi Hasegawa,3 Takeshi Nemoto,1,4 Hiroo Yokozeki,4 Kiyoshi Nishioka,4 Akio Matsukage,2 Misao Ohki,1 and Tsutomu Ohta1*

Center for Medical Genomics,1 Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan,3 Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo, Japan,2 Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan4

Received 15 April 2006/ Returned for modification 17 May 2006/ Accepted 13 December 2006

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.

* Corresponding author. Mailing address: National Cancer Center Research Institute, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan. Phone: 81-3-3542-2511. Fax: 81-3-3248-1631. E-mail: cota{at}gan2.res.ncc.go.jp.

{triangledown} Published ahead of print on 13 November 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

Molecular and Cellular Biology, February 2007, p. 1348-1355, Vol. 27, No. 4
0270-7306/07/$08.00+0     doi:10.1128/MCB.00658-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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