子宮内膜細胞の老化逸脱へのゲノム多様性の関与と癌幹細胞における不死化能獲得機構

• 研究課題/領域番号: 20390435
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 産婦人科学
• 研究機関: 九州大学
• 研究代表者: 和氣 徳夫 九州大学, 医学研究院・生殖病態生理学, 教授 (60091584)
• 研究分担者: 小林 裕明 九州大学, 医学研究院, 准教授 (70260700) ; 福嶋 恒太郎 九州大学, 病院・講師 (40304779) ; 加藤 聖子 順天堂大学, 医学部, 准教授 (10253527)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 19,500千円 (直接経費: 15,000千円、間接経費: 4,500千円); 2010年度: 5,590千円 (直接経費: 4,300千円、間接経費: 1,290千円); 2009年度: 5,200千円 (直接経費: 4,000千円、間接経費: 1,200千円); 2008年度: 8,710千円 (直接経費: 6,700千円、間接経費: 2,010千円)
• キーワード: SNP / AED / ゲノム多様性 / 遺伝子発現制御 / 癌化 / 子宮体癌 / 細胞老化シグナル / Endometrial cancer / 細胞老化誘導シグナロソーム / cancer stem cells / EMT / 癌細胞老化 / Allelic Expression Difference / 子宮内膜幹細胞

研究概要

Ras/ERα/MDM2/p52/p21シグナロソームにはゲノム多様性が存在し対立遺伝子間発現量に差異があることを明らかにした。特にMDM2 p1プロモータ活性にはAEDが関与し、その機能に影響を与えていることが判明した。子宮体癌幹細胞で発現を更新する遺伝子を同定した。そのうち細胞表面で発現するものを標的に抗体を作成し幹細胞を同定するMACSシステムを構築した。

研究成果

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• [雑誌論文] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers. (2010)
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• [雑誌論文] Three cases of acute fatty liver of pregnancy : Postpartum clinical course depends on interval between onset of symptoms and termination of pregnancy (2010)
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• [雑誌論文] Sentinel node detection with (99m)Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (2010)
  • 著者名/発表者名: Ogawa S, Kobayashi H, Amada S, Yahata H, Sonoda K, Abe K, Baba S, Sasaki M, Kaku T, Wake N
  • 雑誌名: Int J Clin Oncol 巻: 15(1) ページ: 52-58
  • NAID: 10027201656
  • 査読あり
• [雑誌論文] Comparative study of peripheral neurotoxicity after injection of two different paclitaxel formulations in rats (2010)
  • 著者名/発表者名: Nakamura I, Ichimura E, Kobayashi H, Mashiba H, Nagai H, Ebara K, Hayashi H, Okamoto K, Wake N, Nishikawa K
  • 雑誌名: Arzneimittel Forschung Drug Research 巻: 60(4) ページ: 205-209
  • 査読あり
• [雑誌論文] A Definitive Haplotype Map as Determined by Genotyping Duplicated Haploid Genomes Finds a Predominant Haplotype Preference at Copy-Number Variation Events (2010)
  • 著者名/発表者名: Kukita Y, Yahara K, Tahira T, Higasa K, Sonoda M, Yamamoto K, Kato K, Wake N, Hayashi K
  • 雑誌名: The American journal of human genetics 巻: 86 ページ: 918-928
  • NAID: 120002239171
  • 査読あり
• [雑誌論文] Coincident expression of beta-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas (2010)
  • 著者名/発表者名: Kurihara S, Oda Y, Ohishi Y, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Mod Pathol 巻: 23(2) ページ: 225-234
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• [雑誌論文] Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage (2010)
  • 著者名/発表者名: Kato K, Takao T, Kuboyama A, Tanaka Y, Ohgami T, Yamaguchi S, Adachi S, Yoneda T, Ueoka, Y, Kato Keiji, Hayashi S, Asanoma K, Wake N
  • 雑誌名: The American Journal of Pathology 巻: 176(1) ページ: 381-392
  • 査読あり
• [雑誌論文] Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain shedding (2010)
  • 著者名/発表者名: Sonoda K, Miyamoto S, Nakashima M, Wake N
  • 雑誌名: Exp Cell Res 巻: 316(11) ページ: 1795-1803
  • NAID: 120005227172
  • 査読あり
• [雑誌論文] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers (2010)
  • 著者名/発表者名: Ohgami T, Kato K, Kobayashi H, Sonoda K, Inoue T, Yamaguchi S, Yoneda T, Wake N :
  • 雑誌名: Cancer Sci 巻: 101(6) ページ: 1387-1395
  • NAID: 10026593277
  • 査読あり
• [雑誌論文] Three cases of acute fatty liver of pregnancy : Postpartum clinical course depends on interval between onset of symptoms and termination of pregnancy (2010)
  • 著者名/発表者名: Aso K, Hojo S, Yumoto Y, Fukushima K, Miyazaki M, Kotoh K, Wake N
  • 雑誌名: J Matern Fetal Neonatal Med 巻: 23(9) ページ: 1047-1049
  • 査読あり
• [雑誌論文] Coincident expression of beta-catenin and cychn D1 in endometrial stromal tumors and related high-grade sarcomas. (2010)
  • 著者名/発表者名: Kurihara S, Oda, Y, Ohishi, Y, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Mod Pathol 23(2) ページ: 225-34
  • 査読あり
• [雑誌論文] Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells (2009)
  • 著者名/発表者名: Takahashi A, Kato K, Kuboyama A, Inoue T, Tanaka Y, Kuhara A, Kinoshita K, Takeda S, Wake N
  • 雑誌名: Gynecologic oncology
• [雑誌論文] Immunohistochemical characterization of mullerian mucinous borderline tumors : possible histogenetic link with serous borderline tumors and low-grade endometrioid tumors (2009)
  • 著者名/発表者名: Yasunaga M, Ohishi Y, Oda Y, Misumi M, Iwasa A, Kurihara S, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Human Pathorogy. 40(7) ページ: 965-974
• [雑誌論文] Homebox gene HOPX is epigenetically silenced in human uterine endometrial cancer cells by inhibiting serum response factor (2009)
  • 著者名/発表者名: Yamaguchi S, Asanoma K, Takao T, Kato K, Wake N
  • 雑誌名: International Journal of Cancer. 124 ページ: 2257-2588
• [雑誌論文] The Level of RCAS1 Expression Is Inversely Correlated With the Number of Vitamin-Positive Stromal Cells in Epithelial Overian Cancer (2009)
  • 著者名/発表者名: Sonoda K, Miyamoto S, Kobayashi H, Ogawa S, Okugawa K, Taniguchi S, Wake N
  • 雑誌名: International Journal of Gynecological Cancer. 19(5) ページ: 838-843
• [雑誌論文] Can we diagnose invasive cervical cancer during pregnancy as precise as in nonpregnant women?: maternal and perinatal outcome in pregnancies complicated with cervical cancers (2009)
  • 著者名/発表者名: Fukushima K, Ogawa S, Tsukimori K, Kobayashi H, Wake N
  • 雑誌名: Int J Gynecol Cancer. 19(8) ページ: 1439-1445
• [雑誌論文] Level of reactive oxygen species induced by p21Waf1/CIP1 is critical for the determination of cell fate (2009)
  • 著者名/発表者名: Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, Ueoka Y, Yamaguchi S, Ohgami T, Wake N
  • 雑誌名: Cancer Science. 100(7) ページ: 1275-1283
  • NAID: 10027192262
• [雑誌論文] Hobnail-like cells in serous borderline tumor do not represent concomitant incipient clear cell neoplasms (2009)
  • 著者名/発表者名: Ohishi Y, Oda Y, Kurihara S, Kaku T, Yasunaga M, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Hum Pathol. 40(8) ページ: 1168-1175
• [雑誌論文] The Phenotypic and Metabolic of Characteristics of Neutrophils in Normal Pregnancy and Preeclampsia (2009)
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  • 雑誌名: Current immunology reviews 5(3) ページ: 243-248
  • 査読あり
• [雑誌論文] Improvement in the outcome of patients with antenatally diagnosed congenital diaphragmatic hernia using gentle ventilation and circulatory stabilization. (2009)
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  • 雑誌名: Pediatric surgery international 25(6) ページ: 487-492
  • NAID: 10029305718
  • 査読あり
• [雑誌論文] Three-dimensional power Doppler sonography in the diagnosis of a cystic sacrococcygeal teratoma mimicking a meningomyelocele : A case report. (2009)
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  • 雑誌名: Journal of clinical ultrasound 37(7) ページ: 410-410
  • 査読あり
• [雑誌論文] Immunohistochemical characterization of mullerian mucino us borderline tumors : possible histogenetic link with serous borderline tumors and low-grade endometrioid tumors. (2009)
  • 著者名/発表者名: Yasunaga M, Ohishi Y, Oda Y, Misumi M, Iwasa A, Kurihara S, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Human Pathorogy 40(7) ページ: 965-974
  • 査読あり
• [雑誌論文] Homebox gene HOPX is epigenetically silenced in human uterine endometrial cancer cells by inhibiting serum response factor (2009)
  • 著者名/発表者名: Yamaguchi S, Asanoma K, Takao T, Kato K, Wake, N.
  • 雑誌名: International Journal of Cancer 124 ページ: 2257-2588
  • 査読あり
• [雑誌論文] The Level of RCAS1 Expression Is Inversely Correlated With the Number of Vitamin-Positive Stromal Cells in Epithelial Overian Cancer (2009)
  • 著者名/発表者名: Sonoda K, Miyamoto S, Kobayashi H, Ogawa S, Okugawa K, Taniguchi S, Wake N
  • 雑誌名: International Journal of Gynecological Cancer 19(5) ページ: 838-843
  • 査読あり
• [雑誌論文] Preload index of the inferior vena cava as a possible predictive marker of hydropic changes in fetuses with Ebstein anomaly (2009)
  • 著者名/発表者名: Hidaka N, Sugitani M, Fujita Y, Fukushima K, Tsukimori K, Wake, N.
  • 雑誌名: J Ultrasound in Medicine 2009 28(10) ページ: 1369-1374
  • 査読あり
• [雑誌論文] Prenatal diagnosis of trisomy 16 mosaicism manifested as pulmonary artery stenosis (2009)
  • 著者名/発表者名: Hidaka N, Yamamoto N, Tsukimori K, Hojo S, Suzuki S, Wake N
  • 雑誌名: J Clin Ultrasound 37(2) ページ: 107-11
  • 査読あり
• [雑誌論文] Can we diagnose invasive cervical cancer during pregnancy as precise as in nonpregnant women? : maternal and perinatal outcome in pregnancies complicated with cervical cancers. (2009)
  • 著者名/発表者名: Fukushima K, Ogawa S, Tsukimori K, Kobayashi H, Wake N
  • 雑誌名: Int J Gynecol Cancer 19(8) ページ: 1439-45
  • 査読あり
• [雑誌論文] Level of reactive oxygen species induced by p21Waf1/CIP1 is critical for the determination of cell fate (2009)
  • 著者名/発表者名: Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, UeokaY, Yamaguchi S, Ohgami T, Wake N
  • 雑誌名: Cancer Science 100(7) ページ: 1275-83
  • NAID: 10027192262
  • 査読あり
• [雑誌論文] Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung (2008)
  • 著者名/発表者名: Yasunaga M, Ohishi Y, Nishimura I, Tamiya S, Iwasa A, Takagi E, Inoue T, Yahata, H, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Pathology International. 58(4) ページ: 244-248
  • NAID: 10027376338
• [雑誌論文] CD10 immunostaining distinguishes atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) from endometrial carcinoma invading the myometrium (2008)
  • 著者名/発表者名: Tanaka Y, Kato K, Mibu R, Uchida S, Asanoma Ohishi Y, Kaku T, Kobayashi H, Aishima S, Umekita Y, Wake N, Tsuneyoshi M
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• [雑誌論文] Interstitial pregnancy in a woman with congenital afibrinogenemia. (2008)
  • 著者名/発表者名: Matsushita I, Uchida S, Yamaguchi A, Tanaka Y, Ogawa S, Kato K, Tsukimori K, Wake N
  • 雑誌名: The journal of obstetrics and gynaecology research. 34(59) ページ: 442-453
  • NAID: 10022603879
• [雑誌論文] Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting serum response factor (2008)
  • 著者名/発表者名: Yakaguchi S, Asanoma K, Tanaka T, Kato K, Wake N
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• [雑誌論文] Endometrial stromal sarcomas and related high-grade sarcomas : immunohistochemical and molecular genetic study of 31 cases (2008)
  • 著者名/発表者名: Kurihara S, Oda Y, Ohishi Y, Iwasa A, Takahira T, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: The American Journal of Surgical Pathology. 32(8) ページ: 1228-1238
• [雑誌論文] CDIO Immunostaining distinguishes atypical polypoid adenomyofibroma(atypical polypoid adenomyoma)from endometrial carcinoma invading the myometrium. (2008)
  • 著者名/発表者名: Ohishi Y, Kaku T, Kobayashi H, Aishima S, Umekita Y, Wake N, Tsuneyoshi M
  • 雑誌名: Human Pathology 39 ページ: 1446-1453
  • 査読あり
• [雑誌論文] Biological role of the unique molecule RCAS1: A bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis. (2008)
  • 著者名/発表者名: Sonoda K, Miyamoto S, Nakashima M, Wake N
  • 雑誌名: Frontiers in Bioscience. 13(1) ページ: 1106-1116
  • 査読あり
• [雑誌論文] Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung (2008)
  • 著者名/発表者名: Yasunaga M, Ohishi Y, Nishimura I, Tamiya S, Iwasa A, Takagi E, Inoue T, Yahata H, Kobayashi H, Wake N, Tsuneyoshi M.
  • 雑誌名: Pathology international. 58(4) ページ: 244-248
  • NAID: 10027376338
  • 査読あり
• [雑誌論文] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression. (2008)
  • 著者名/発表者名: Tanaka Y, Kato K, Mibu R, Uchida S, Asanoma K, Hashimoto K, Nozaki M, Wake N.
  • 雑誌名: Menopause 15(3) ページ: 442-453
  • 査読あり
• [雑誌論文] Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53-and pl6/Rb-dependent cell cycle regulator proteins (2008)
  • 著者名/発表者名: Iwasa A, Oda S, Kurihara S, Ohishi Y, Yasunaga M, Nishimura I, Takagi E, Kobayashi H, Wake N, Tsuneyoshi M
  • 雑誌名: Pathology International 56 ページ: 757-764
  • 査読あり
• [雑誌論文] Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting serum response factor (2008)
  • 著者名/発表者名: Shinichiro Yamaguchil, Kazuo Asanoma, Tomoka Takaol, Kiyoko Kato, Norio Wake
  • 雑誌名: Int. J. Cancer In press
  • 査読あり
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