Genome diversity associated with in montalization and establishment of endometrial cancer stem cell isolation

• Project/Area Number: 20390435
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyushu University
• Principal Investigator: WAKE Norio Kyushu University, 医学研究院・生殖病態生理学, 教授 (60091584)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Hiroaki 九州大学, 医学研究院, 准教授 (70260700) ; FUKUSHIMA Kotaro 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)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: 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

Research Abstract

There is genome diversity in Ras/ERα/MDM2/p53/p21 signalosome. Genome diversity in these signalosome influences each gene function due to allelic expression difference. AED of MDM2 p1 promoter activity is defected frequently and influences MDM2 gene function in several genes are upregulated in endometrial cancer stem cells. Among these genes, antibodies are prepared against gene products expressed in all surface, establishing the efficient method to identify the cancer stem cells.

Research Products

• [Journal Article] Expression and localization of E-cadherin and catenin in uterine carcinosarcoma (2011)
  • Author(s): Nishimura I, Ohishi Y, Oda Y, Kishimoto J, Yasunaga M, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Virchows Arch Volume: 458(1) Pages: 85-94
  • Peer Reviewed
• [Journal Article] Incidence of postmolar gestational trophoblastic disease in androgenetic moles and the morphological features associated with low risk postmolar gestational trophoblastic disease (2011)
  • Author(s): Kaneki E, Kobayashi H, Hirakawa T, Matsuda T, Kato H, Wake N
  • Journal Title: Cancer Sci Volume: 101(7) Pages: 1717-1721
  • NAID: 10026595031
  • Peer Reviewed
• [Journal Article] Cytoplasmic and stromal expression of laminin 2 chain correlates with infiltrative invasion in ovarian mucinous neoplasms of gastro-intestinal type (2011)
  • Author(s): Okuma E, Ohishi Y, Oda Y, Aishima S, Kurihara S, Nishimural, Yasunaga M, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Oncol Rep Volume: 24(6) Pages: 1569-1576
  • Peer Reviewed
• [Journal Article] Nuclear localization of E-cadherin but not beta-catenin in human ovarian granulosa cell tumours and normal ovarian follicles and ovarian stroma (2011)
  • Author(s): Ohishi Y, Oda Y, Kurihara S, Kaku T, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Histopathology Volume: 58(3) Pages: 423-432
  • Peer Reviewed
• [Journal Article] Sentinel node detection with (99m)Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (2010)
  • Author(s): Ogawa S, Kobayashi H, Amada S, Yahata H, Sonoda K, Abe K, Baba S, Sasaki M, Kaku T, Wake N
  • Journal Title: Int J Clin Oncol. 15(1) Pages: 52-58
  • NAID: 10027201656
• [Journal Article] A Definitive Haplotype Map as Determined by Genotyping Duplicated Haploid Genomes Finds a Predominant Haplotype Preference at Copy-Number Variation Events (2010)
  • Author(s): Kukita Y, Yahara K, Tahira T, Higasa K, Sonoda M, Yamamoto K, Kato K, Wake N, Hayashi K
  • Journal Title: The American journal of human genetics. 86 Pages: 918-928
  • NAID: 120002239171
• [Journal Article] Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage (2010)
  • Author(s): 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
  • Journal Title: The American Journal of Pathology. 176(1) Pages: 381-392
• [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers. (2010)
  • Author(s): Ohgami T, Kato K, Kobayashi H, Sonoda K, Inoue T, Yamaguchi S, Yoneda T, Wake N
  • Journal Title: Cancer Sci. 101(6) Pages: 1387-1395
  • NAID: 10026593277
• [Journal Article] Abnormal fetal movements, micrognathia and pulmonary hypoplasia : a case report. (2010)
  • Author(s): Morokuma S, Anami A, Tsukimori K, Fukushima K, Wake N.
  • Journal Title: Abnormal fetal movements : BMC Pregnancy & Childbirth1-3
• [Journal Article] Three cases of acute fatty liver of pregnancy : Postpartum clinical course depends on interval between onset of symptoms and termination of pregnancy (2010)
  • Author(s): Aso K, Hojo S, Yumoto Y, Fukushima K, Miyazaki M, Kotoh K, Wake N.
  • Journal Title: J Matern Fetal Neonatal Med. 23(9) Pages: 1047-1049
• [Journal Article] Sentinel node detection with (99m)Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (2010)
  • Author(s): Ogawa S, Kobayashi H, Amada S, Yahata H, Sonoda K, Abe K, Baba S, Sasaki M, Kaku T, Wake N
  • Journal Title: Int J Clin Oncol Volume: 15(1) Pages: 52-58
  • NAID: 10027201656
  • Peer Reviewed
• [Journal Article] Comparative study of peripheral neurotoxicity after injection of two different paclitaxel formulations in rats (2010)
  • Author(s): Nakamura I, Ichimura E, Kobayashi H, Mashiba H, Nagai H, Ebara K, Hayashi H, Okamoto K, Wake N, Nishikawa K
  • Journal Title: Arzneimittel Forschung Drug Research Volume: 60(4) Pages: 205-209
  • Peer Reviewed
• [Journal Article] A Definitive Haplotype Map as Determined by Genotyping Duplicated Haploid Genomes Finds a Predominant Haplotype Preference at Copy-Number Variation Events (2010)
  • Author(s): Kukita Y, Yahara K, Tahira T, Higasa K, Sonoda M, Yamamoto K, Kato K, Wake N, Hayashi K
  • Journal Title: The American journal of human genetics Volume: 86 Pages: 918-928
  • NAID: 120002239171
  • Peer Reviewed
• [Journal Article] Coincident expression of beta-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas (2010)
  • Author(s): Kurihara S, Oda Y, Ohishi Y, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Mod Pathol Volume: 23(2) Pages: 225-234
  • Peer Reviewed
• [Journal Article] Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage (2010)
  • Author(s): 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
  • Journal Title: The American Journal of Pathology Volume: 176(1) Pages: 381-392
  • Peer Reviewed
• [Journal Article] Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain shedding (2010)
  • Author(s): Sonoda K, Miyamoto S, Nakashima M, Wake N
  • Journal Title: Exp Cell Res Volume: 316(11) Pages: 1795-1803
  • NAID: 120005227172
  • Peer Reviewed
• [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers (2010)
  • Author(s): Ohgami T, Kato K, Kobayashi H, Sonoda K, Inoue T, Yamaguchi S, Yoneda T, Wake N :
  • Journal Title: Cancer Sci Volume: 101(6) Pages: 1387-1395
  • NAID: 10026593277
  • Peer Reviewed
• [Journal Article] Three cases of acute fatty liver of pregnancy : Postpartum clinical course depends on interval between onset of symptoms and termination of pregnancy (2010)
  • Author(s): Aso K, Hojo S, Yumoto Y, Fukushima K, Miyazaki M, Kotoh K, Wake N
  • Journal Title: J Matern Fetal Neonatal Med Volume: 23(9) Pages: 1047-1049
  • Peer Reviewed
• [Journal Article] Coincident expression of beta-catenin and cychn D1 in endometrial stromal tumors and related high-grade sarcomas. (2010)
  • Author(s): Kurihara S, Oda, Y, Ohishi, Y, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Mod Pathol 23(2) Pages: 225-34
  • Peer Reviewed
• [Journal Article] Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells (2009)
  • Author(s): Takahashi A, Kato K, Kuboyama A, Inoue T, Tanaka Y, Kuhara A, Kinoshita K, Takeda S, Wake N
  • Journal Title: Gynecologic oncology
• [Journal Article] Immunohistochemical characterization of mullerian mucinous borderline tumors : possible histogenetic link with serous borderline tumors and low-grade endometrioid tumors (2009)
  • Author(s): Yasunaga M, Ohishi Y, Oda Y, Misumi M, Iwasa A, Kurihara S, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Human Pathorogy. 40(7) Pages: 965-974
• [Journal Article] Homebox gene HOPX is epigenetically silenced in human uterine endometrial cancer cells by inhibiting serum response factor (2009)
  • Author(s): Yamaguchi S, Asanoma K, Takao T, Kato K, Wake N
  • Journal Title: International Journal of Cancer. 124 Pages: 2257-2588
• [Journal Article] The Level of RCAS1 Expression Is Inversely Correlated With the Number of Vitamin-Positive Stromal Cells in Epithelial Overian Cancer (2009)
  • Author(s): Sonoda K, Miyamoto S, Kobayashi H, Ogawa S, Okugawa K, Taniguchi S, Wake N
  • Journal Title: International Journal of Gynecological Cancer. 19(5) Pages: 838-843
• [Journal Article] 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)
  • Author(s): Fukushima K, Ogawa S, Tsukimori K, Kobayashi H, Wake N
  • Journal Title: Int J Gynecol Cancer. 19(8) Pages: 1439-1445
• [Journal Article] Level of reactive oxygen species induced by p21Waf1/CIP1 is critical for the determination of cell fate (2009)
  • Author(s): Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, Ueoka Y, Yamaguchi S, Ohgami T, Wake N
  • Journal Title: Cancer Science. 100(7) Pages: 1275-1283
  • NAID: 10027192262
• [Journal Article] Hobnail-like cells in serous borderline tumor do not represent concomitant incipient clear cell neoplasms (2009)
  • Author(s): Ohishi Y, Oda Y, Kurihara S, Kaku T, Yasunaga M, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Hum Pathol. 40(8) Pages: 1168-1175
• [Journal Article] The Phenotypic and Metabolic of Characteristics of Neutrophils in Normal Pregnancy and Preeclampsia (2009)
  • Author(s): Tsukimori K, Fukushima K, NakanoH, Wake N
  • Journal Title: Current immunology reviews 5(3) Pages: 243-248
  • Peer Reviewed
• [Journal Article] Improvement in the outcome of patients with antenatally diagnosed congenital diaphragmatic hernia using gentle ventilation and circulatory stabilization. (2009)
  • Author(s): Masumoto K, Teshiba R, Esumi G, Nagata K, Takahata Y, Hikino S, Hara T, Hojo S, Tsukimori K, Wake N, Kinukawa N, Taguchi T
  • Journal Title: Pediatric surgery international 25(6) Pages: 487-492
  • NAID: 10029305718
  • Peer Reviewed
• [Journal Article] Three-dimensional power Doppler sonography in the diagnosis of a cystic sacrococcygeal teratoma mimicking a meningomyelocele : A case report. (2009)
  • Author(s): Sugitani M, Morokum S, Hidaka N, Kinoshita Y, Taguchi T, Tsukimori K, Wake N
  • Journal Title: Journal of clinical ultrasound 37(7) Pages: 410-410
  • Peer Reviewed
• [Journal Article] Immunohistochemical characterization of mullerian mucino us borderline tumors : possible histogenetic link with serous borderline tumors and low-grade endometrioid tumors. (2009)
  • Author(s): Yasunaga M, Ohishi Y, Oda Y, Misumi M, Iwasa A, Kurihara S, Nishimura I, Okuma E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Human Pathorogy 40(7) Pages: 965-974
  • Peer Reviewed
• [Journal Article] Homebox gene HOPX is epigenetically silenced in human uterine endometrial cancer cells by inhibiting serum response factor (2009)
  • Author(s): Yamaguchi S, Asanoma K, Takao T, Kato K, Wake, N.
  • Journal Title: International Journal of Cancer 124 Pages: 2257-2588
  • Peer Reviewed
• [Journal Article] The Level of RCAS1 Expression Is Inversely Correlated With the Number of Vitamin-Positive Stromal Cells in Epithelial Overian Cancer (2009)
  • Author(s): Sonoda K, Miyamoto S, Kobayashi H, Ogawa S, Okugawa K, Taniguchi S, Wake N
  • Journal Title: International Journal of Gynecological Cancer 19(5) Pages: 838-843
  • Peer Reviewed
• [Journal Article] Preload index of the inferior vena cava as a possible predictive marker of hydropic changes in fetuses with Ebstein anomaly (2009)
  • Author(s): Hidaka N, Sugitani M, Fujita Y, Fukushima K, Tsukimori K, Wake, N.
  • Journal Title: J Ultrasound in Medicine 2009 28(10) Pages: 1369-1374
  • Peer Reviewed
• [Journal Article] Prenatal diagnosis of trisomy 16 mosaicism manifested as pulmonary artery stenosis (2009)
  • Author(s): Hidaka N, Yamamoto N, Tsukimori K, Hojo S, Suzuki S, Wake N
  • Journal Title: J Clin Ultrasound 37(2) Pages: 107-11
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): Fukushima K, Ogawa S, Tsukimori K, Kobayashi H, Wake N
  • Journal Title: Int J Gynecol Cancer 19(8) Pages: 1439-45
  • Peer Reviewed
• [Journal Article] Level of reactive oxygen species induced by p21Waf1/CIP1 is critical for the determination of cell fate (2009)
  • Author(s): Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, UeokaY, Yamaguchi S, Ohgami T, Wake N
  • Journal Title: Cancer Science 100(7) Pages: 1275-83
  • NAID: 10027192262
  • Peer Reviewed
• [Journal Article] Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung (2008)
  • Author(s): Yasunaga M, Ohishi Y, Nishimura I, Tamiya S, Iwasa A, Takagi E, Inoue T, Yahata, H, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Pathology International. 58(4) Pages: 244-248
  • NAID: 10027376338
• [Journal Article] CD10 immunostaining distinguishes atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) from endometrial carcinoma invading the myometrium (2008)
  • Author(s): Tanaka Y, Kato K, Mibu R, Uchida S, Asanoma Ohishi Y, Kaku T, Kobayashi H, Aishima S, Umekita Y, Wake N, Tsuneyoshi M
  • Journal Title: Human Pathology. 39(10) Pages: 1446-1453
• [Journal Article] Interstitial pregnancy in a woman with congenital afibrinogenemia. (2008)
  • Author(s): Matsushita I, Uchida S, Yamaguchi A, Tanaka Y, Ogawa S, Kato K, Tsukimori K, Wake N
  • Journal Title: The journal of obstetrics and gynaecology research. 34(59) Pages: 442-453
  • NAID: 10022603879
• [Journal Article] 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)
  • Author(s): Yakaguchi S, Asanoma K, Tanaka T, Kato K, Wake N
  • Journal Title: International journal of cancer. 124(11) Pages: 2577-2588
• [Journal Article] Endometrial stromal sarcomas and related high-grade sarcomas : immunohistochemical and molecular genetic study of 31 cases (2008)
  • Author(s): Kurihara S, Oda Y, Ohishi Y, Iwasa A, Takahira T, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: The American Journal of Surgical Pathology. 32(8) Pages: 1228-1238
• [Journal Article] CDIO Immunostaining distinguishes atypical polypoid adenomyofibroma(atypical polypoid adenomyoma)from endometrial carcinoma invading the myometrium. (2008)
  • Author(s): Ohishi Y, Kaku T, Kobayashi H, Aishima S, Umekita Y, Wake N, Tsuneyoshi M
  • Journal Title: Human Pathology 39 Pages: 1446-1453
  • Peer Reviewed
• [Journal Article] Biological role of the unique molecule RCAS1: A bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis. (2008)
  • Author(s): Sonoda K, Miyamoto S, Nakashima M, Wake N
  • Journal Title: Frontiers in Bioscience. 13(1) Pages: 1106-1116
  • Peer Reviewed
• [Journal Article] Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung (2008)
  • Author(s): Yasunaga M, Ohishi Y, Nishimura I, Tamiya S, Iwasa A, Takagi E, Inoue T, Yahata H, Kobayashi H, Wake N, Tsuneyoshi M.
  • Journal Title: Pathology international. 58(4) Pages: 244-248
  • NAID: 10027376338
  • Peer Reviewed
• [Journal Article] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression. (2008)
  • Author(s): Tanaka Y, Kato K, Mibu R, Uchida S, Asanoma K, Hashimoto K, Nozaki M, Wake N.
  • Journal Title: Menopause 15(3) Pages: 442-453
  • Peer Reviewed
• [Journal Article] Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53-and pl6/Rb-dependent cell cycle regulator proteins (2008)
  • Author(s): Iwasa A, Oda S, Kurihara S, Ohishi Y, Yasunaga M, Nishimura I, Takagi E, Kobayashi H, Wake N, Tsuneyoshi M
  • Journal Title: Pathology International 56 Pages: 757-764
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): Shinichiro Yamaguchil, Kazuo Asanoma, Tomoka Takaol, Kiyoko Kato, Norio Wake
  • Journal Title: Int. J. Cancer In press
  • Peer Reviewed
• [Remarks] ホームページ等