2005 Fiscal Year Final Research Report Summary
SSX : New Molecular Target of Bone and Soft Tissue Tumor
| Project/Area Number |
16591520
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka Medical Center for Cancer and Cardiovascular Diseases |
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Principal Investigator |
YOSHIOKA Kiyoko Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Chief Investigator, 研究所, 主任研究員 (40342993)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Kazuyuki Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Department Head, 研究所, 部長 (20301806)
YOSHIKAWA Hideki Osaka University Graduate School of Medicine, Orthopedic Surgery, Professor, 大学院・医学研究科, 教授 (60191558)
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| Project Period (FY) |
2004 – 2005
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| Keywords | SSX / invasion / osteosarcoma / colony formation / tumor formation / siRNA / cancer / testis antigen / NASBA |
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| Research Abstract |
The SSX genes were initially identified as fusion partners to the SYT gene in human synovial sarcomas carrying a recurrent t (X;18)(p11.2;q11.2) chromosomal translocation. Besides adult human testis, SSX genes were expressed at varying frequencies in numbers of malignancies thereby categorized as cancer/testis antigens. Using nucleic acid sequence-based amplification, we have reported that the expression level in the malignant tumors (3.8±1.4 copies/μg of total RNA in log10 order) was significantly higher than that in the benign tumors (2.4±0.5,p<0.0001). In order to examine the biological function of SSX, we firstly made stable transfectants with wild type SSX using human osteosarcoma cell line, Saos-2, which moderately expressed SSX. The expression of SSX was mainly localized in the nucleus with patched pattern. The SSX transfectants promoted colony formation in soft agar and tumor formation in nude mice, but showed little change in growth rate in 2D culture. The transfectants also increased motility, chemotaxis and invasiveness using scratch wound assay and Boyden chamber assay. Since the C-terminal region of SSX strongly bound to Histone in the nucleus, we next made stable transfectants with C-terminal deletion mutants of SSX1,using human fibrosarcoma cell line, HT1080, which highly expressed endogenous SSX1. The transfectants showed marked stress fibers and focal adhesions, decreased motility, chemotaxis and invasiveness in vitro, and attenuated tumorigenesis in nude mice. Furthermore, the lowering of the endogenous expression of SSX1 in HT1080 cells by the treatment with specific siRNA markedly decreased chemotaxis, but did not affect cellular proliferation. Collectively, these data suggested that SSX protein regulated several gene expressions leading to the tumor invasion, and could be a new molecular target under clinical setting.
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[Journal Article] Quantification of SSX mRNA expression in human bone and soft tissue tumors using Nucleic Acid Sequence-Based Amplification (NASBA)2005
Author(s)
Naka, N., Joyama, S., Tsukamoto, Y., Yoshioka, K., Hashimoto, N., Ujiiye T., Hayashi, T., Kawase, M., Mano, M., Ishiguro, S., Myoui, A., Ueda, T., Yoshikawa, H., Araki, N., Itoh, K.
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Journal Title
J.Mol.Diagn. 7
Pages: 187-197
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intrathecal administration of Y-2 7632,a specific ROCK inhibitor, for rat neoplastic meningitis2005
Author(s)
Nakagawa, H., Yoshioka, K., Miyahara, E., Fukushima, Y, Tamura, M., Itoh, K.
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Journal Title
Mol.Cancer.Res. 3(cited on the cover)
Pages: 425-433
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Multiple signaling pathways are activated during Insulin-like growth factor-I (IGF-I) stimulated breast cancer cell migration2005
Author(s)
Zhang, X., Lin, M., van Golen, KL, Yoshioka, K., Itoh K., Yee, D.
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Journal Title
Breast Cancer Res.Treat. 93
Pages: 159-168
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] IL-6/soluble IL-6R Signaling Attenuates Proliferation and Invasion, and Induces Morphological Changes of a Newly Established Pleomorphic Malignant Fibrous Histiocytoma Cell Line2004
Author(s)
Nakanishi, H.Yoshioka, K., Joyama S., Araki, N., Myoui, A., Ishiguro, S., Ueda, T., Yoshikawa, H., Itoh, K.
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Journal Title
Am.J.Pathol. 165
Pages: 471-480
Description
「研究成果報告書概要(欧文)」より
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