2007 Fiscal Year Final Research Report Summary
EVALUATION OF GRADE OF MALIGNANCY AND ITS CLINICAL USE ON THE BASIS OF SFRP METHYLATION IN ORAL SQUAMOUS CELL CARCINOMA
| Project/Area Number |
18592223
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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 |
Surgical dentistry
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
HIRATSUKA Hiroyoshi Sapporo Medical University, DPT OF ORAL SURG, SCHOOL OF MEDICINE, PROFESSOR (50165180)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Akihiro SAPPORO MEDICAL UNIVERSITY, 医学部, ASSOCIATE PROFESSOR (10305237)
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| Project Period (FY) |
2006 – 2007
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| Keywords | cancer / genomics / Wnt signaling pathway / dentistry |
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| Research Abstract |
Although mutations of APC, CTNNB1 (β-catenin) and AXIN1 are rare in oral squamous cell carcinoma (OSCC), activation of the Wnt signaling pathway is thought to play an important role in oral carcinogenesis. In the present study, we examined the relationship between Wnt signaling and epigenetic alteration of the secreted frizzled-related protein (SFRP) genes in OSCC. We frequently detected loss of menbrane localization of β-catenin and its cytoplasmic or nuclear accumulation in OSCC cell lines, although these cell lines showed no APC or CTNNB1 (β-catenin) mutations and no methylation of CDH1 (E-cadherin). By contrast, we frequently detected methylation of SFRP1 (7/17, 41%), SFRP2 (16/17, 94%) and SFRP5 (14/17, 82%) in a panel of OSCC cell lines, as well as in specimens of primary tumors collected from 44 OSCC patients (SFRP1, 10/42, 24%; SFRP2, 16/44, 36%; SFRP5, 7/43, 16%). We also observed that OSCC cell lines express various Wnt ligands, and that ectopic expression of SFRPs inhibited cancer cell proliferation. Our results confirm the frequent methylation and silencing of SFRP genes in OSCC, and suggest, that their loss of function contributes to activation of Wnt signaling that leads to cell proliferation during oral carcinogenesis.
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[Journal Article] Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma2008
Author(s)
Sogabe, Y., Suzuki, H., Toyota, M., Ogi, K., Imai, T., Nojima, M., Sasaki, Y., Hiratsuka, H., Tokino, T
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[Journal Article] Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma2008
Author(s)
Imai, T., Toyota, M., Suzuki, H., Akino, K., Ogi, K., Sogabe, Y., Kashima, L., Maruyama, R., Nojima, M., Mita, H., Sasaki, Y., Itoh, F., Imai, K., Shinomura, Y., Hiratsuka, H., Tokino, T
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[Journal Article] A single-institute phase I/II trial combining nedaplatin dose escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma2008
Author(s)
Miyazaki, A., Kobayashi, J., Yamatoto, T., Kido, Y., Takemura, K., Abe, M., Tomihara, K., Dehari, H., Nakamori, K., Nagai, I., Hiratsuka, H
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[Journal Article] Cytoplasmic RASSF2A is a Pro-apoptotic mediator whose expression is epigenetically silenced in gastric cancer2008
Author(s)
Maruyama, R., Akino, K., Suzuki, H., Imai, T., Ohe-Toyota, M., Yamamoto, E., Nojima, M., Fujikane, T., Sasaki, Y., Yamashita, T., Watanabe, Y., Hiratsuka, H., Hirata, K., Itoh, F., Imai, K., Shinomura, Y., Tokino, T
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Journal Title
Carcinogenesis (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] PRDM5 identified as a target of epigtnetic silencing in colorectal and gastric cancer2007
Author(s)
Watanabe, Y., Toyota, M., Kondo, Y., Suzuki, H., Imai, T., Ohe-Toyota, M., Maruyama, R., Nojima, M., Sasaki, Y., Sekido, Y., Hiratsuka, H., Shinomura, Y., Imai, K., Itoh, F., Tokino, T
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Journal Title
Clin Cancer Res 13(16)
Pages: 4786-4794
Description
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[Journal Article] Efficient Cross-Presentation by Heat Shock Protein 90 Peptide Complex-Loaded Dendritic Cells via an Endosomal Pathway2007
Author(s)
Kurotaki, T., Tamura, Y., Ueda, G., Oura, J., Kutami, G., Hirohashi, Y., Sahara, H., Torigoe, T., Hiratsuka, H., Sunakawa, H., Hirata, K., Sato, N
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J Immunol 179(3)
Pages: 1803-1813
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[Journal Article] Gene transfer the CD-40-ligand to human dendritic cells ifichices NK-medjated antitumor effects against human carcinoma cells2007
Author(s)
Tomihara, K., Kato, K., Masuta, Y., Nakamura, K., Tanaka, T., Hiratsuka, H., Hamada, H
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Journal Title
Int J Cancer 120(7)
Pages: 1491-1498
Description
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[Journal Article] Aberrant expression of β- and γ-catenin are independent prognostic markers in oral squamous cell carcinoma2006
Author(s)
Ueda, G., Sunakawa, H., Nakamori, K., Shinya, T., Tsuhako, W., Tamura, Y., Kosugi, T., Sato, N., Ogi, K., Hiratsuka, H
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Int J Oral Maxillofac Surg 35(4)
Pages: 356-61
Description
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