Modification of DNA damage detecting method, Terminal transferase dependent PCR(TDPCR), and its application to endometrial carcinogenesis

• Project/Area Number: 22659298
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: SHIOZAWA Tanri 信州大学, 医学部, 教授 (20235493)
• Co-Investigator(Kenkyū-buntansha): HORIUCHI Akiko 信州大学, 医学部附属病院, 特任研究員 (80334895) ; SUZUKI Akihisa 信州大学, 医学部, 助教 (10547095)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥2,530,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 遺伝子損傷 / TDPCR / 子宮内膜癌 / サイクリン / 子官内膜癌

Research Abstract

The involvement of estrogen in endometrial carcinogenesis is controversial、therefore, we intended to examine estrogen or its metabolite could induce DNA damage on endometrial cells by using terminal transferase dependent PCR(TDPCR) method. At first, we modified TDPCR by applying a capillary sequencer and consequently we could avoid its complicated, time-consuming process. By using modified TDPCR, we found that catechol estrogen caused DNA damages on frequently mutated gene in endometrial carcinoma, PTEN, while estrogen did not. In addition, the foci of DNA damage corresponded to known mutation site of PTEN in endometrial carcinoma. Taken together, these data suggest that metabolite of estrogen is responsible for PTEN mutations in endometrial carcinogenesis.

Research Products

• [Journal Article] Involvement of proteasomeβ1i subunit, LMP2, on development of uterin leiomyosarcma (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Shiozawa T, Kanai Y, Yaegashi N, Aburatani H, Tonegawa S, Konishi I
  • Journal Title: N Am J Med Sci Volume: 3(9) Pages: 394-9
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as tumor-suppressor defines new targets for uterin leiomyosarcoma therapy (2011)
  • Author(s): ayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Sudo T, TagawaY, Nishimura R, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Konishi I
  • Journal Title: Sci Rep Volume: 1 Pages: 180-180
  • NAID: 120007110570
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of keratan sulfate : a possible diagnostic markerfor carcinomas of the female genital tract (2011)
  • Author(s): Miyamoto T, Ishii K, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T
  • Journal Title: J Clin Pathol Volume: 64(12)
  • NAID: 120007107373
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of a specific receptor for lipocalin2(solutecarrier family 22 member 17, SLC22A17) and its prognostic significance inendometrial carcinoma (2011)
  • Author(s): Miyamoto T, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T
  • Journal Title: Exp Mol Pathol Volume: 91(2) Pages: 563-8
  • Peer Reviewed
• [Journal Article] Preoperative differential diagnosis of minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia of the uterine cervix : a multicenter study of clinicopathology and magnetic resonanceimaging findings (2011)
  • Author(s): Takatsu A, Shiozawa T, Miyamoto T, Kurosawa K, Kashima H, Yamada T, Kaku T, Mikami Y, Kiyokawa T, Tsuda H, Ishii K, Togashi K, Koyama T, Fujinaga Y, KadoyaM, Hashi A, Susumu N, Konishi I
  • Journal Title: Int J Gynecol Cancer Pages: 1287-96
  • Peer Reviewed
• [Journal Article] Molecular Approach to Uterine Leiomyosarcoma : LMP2-Deficient Mice as an Animal Model of Spontaneous Uterine Leiomyosarcoma (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I
  • Journal Title: Sarcoma Pages: 476-498
  • Peer Reviewed
• [Journal Article] Laser-captured microdissection-microarray analysis of the genes involved in endometrial carcinogenesis : stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance (2011)
  • Author(s): Miyamoto T, Kashima H, Suzuki A, Kikuchi N, Konishi I, Seki N, Shiozawa T
  • Journal Title: Hum Pathol Volume: 42(9) Pages: 1265-74
  • NAID: 120007107405
  • Peer Reviewed
• [Journal Article] ホルモンエストロゲンと子宮内膜癌 (2011)
  • Author(s): 宮本強, 塩沢丹里
  • Journal Title: 産婦人科治療 Volume: 103(4) Pages: 422-429
  • NAID: 40019011934
  • Peer Reviewed
• [Journal Article] 婦人科悪性腫瘍に対するホルモン療法 (2011)
  • Author(s): 宮本強, 塩沢丹里
  • Journal Title: 内分泌外科=Endocrine surgery Volume: 28(3) Pages: 152-156
  • NAID: 10029862393
  • Peer Reviewed
• [Journal Article] Distinguishing primary from secondary mucinous ovarian tumors : an algorithm using the novel marker DPEP1 (2011)
  • Author(s): Okamoto T, Matsumura N, Mandai M, Oura T, Yamanishi Y, Horiuchi A, Hamanishi J, Baba T, Koshiyama M, Shiozawa T, Konishi I
  • Journal Title: Mod Pathol Volume: 24(2) Pages: 267-76
  • Peer Reviewed
• [Journal Article] Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer : a proposal for patient selection (2010)
  • Author(s): Satoh T, Hatae M, Watanabe Y, Yaegashi N, Ishiko O, Kodama S, Yamaguchi S, Ochiai K, Takano M, Yokota H, Kawakami Y, Nishimura S, Ogishima D, Nakagawa S, Kobayashi H, Shiozawa T, Nakanishi T, Kamura T, Konishi I, Yoshikawa H
  • Journal Title: J Clin Oncol Volume: 28(10) Pages: 1727-32
  • Peer Reviewed
• [Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic grade and degree of differentiation (2010)
  • Author(s): Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I
  • Journal Title: Am J Surg Pathol Pages: 1842-8
  • Peer Reviewed
• [Journal Article] Fetal goitrous hypothyroidism due to maternalthyroid stimulation-blocking antibody : a case report (2010)
  • Author(s): Ohira S, Miyake M, Kobara H, Kikuchi N, Osada R, Ashida T, Hirabayashi K, Nishio S, Kanai M, Shiozawa T
  • Journal Title: Fetal Diagn Ther Volume: 28(4) Pages: 220-4
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of histone deacetylases in endometrial carcinoma : involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells (2010)
  • Author(s): Fakhry H, Miyamoto T, Kashima H, Suzuki A, Ke H, Konishi I, Shiozawa T
  • Journal Title: Hum Pathol Volume: 41(6) Pages: 848-58
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of steroid receptor cofactors in ovarian endometriosis : involvement of down-regulated SRC-1 expression in the limitedgrowth activity of the endometriotic epithelium (2010)
  • Author(s): Suzuki A, Horiuchi A, Oka K, Miyamoto T, Kashima H, Shiozawa T
  • Journal Title: Virchows Arch Volume: 456(4) Pages: 433-41
  • Peer Reviewed
• [Journal Article] Type-specific roles of histone deacetylase(HDAC) overexpression inovarian carcinoma : HDAC1 enhances cell proliferation and HDAC3 stimulates cellmigration with downregulation of E-cadherin (2010)
  • Author(s): Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, Konishi I, Shiozawa T
  • Journal Title: Int J Cancer Pages: 1332-46
  • Peer Reviewed
• [Journal Article] Shiozawa T. Cyclin A2 confers cisplatin resistance to endometrial carcinoma cells via up-regulation of an Akt-binding protein, periplakin (2010)
  • Author(s): Suzuki A, Horiuchi A, Ashida T, Miyamoto T, Kashima H, Nikaido T, Konishi I
  • Journal Title: J Cell Mol Med Volume: 14(9) Issue: 9 Pages: 2305-17
  • DOI: 10.1111/j.1582-4934.2009.00839.x
  • Peer Reviewed
• [Journal Article] 長期経過観察中に子宮体癌に進行したatypical polypoid adenomyomaの1例 (2010)
  • Author(s): 宮本強, 布施谷千穂, 石川香織, 鹿島大靖, 堀内晶子, 塩沢丹里
  • Journal Title: 産婦人科の実際 Volume: 59(5) Pages: 845-850
  • Peer Reviewed
• [Journal Article] 産後の大量出血に対して遺伝子組換え活性型血液凝固第VII因子製剤を投与した1例 (2010)
  • Author(s): 大平哲史, 古川哲平, 小原久典, 菊地範彦, 長田亮介, 芦田敬, 金井誠, 塩沢丹里
  • Journal Title: 産婦人科の実際 Volume: 59(7) Pages: 1141-1145
  • Peer Reviewed
• [Journal Article] 常位胎盤早期剥離・胎児死亡例の経膣分娩管理の検討 (2010)
  • Author(s): 菊地範彦, 小原久典, 長田亮介, 大平哲史, 芦田敬, 金井誠, 塩沢丹里
  • Journal Title: 日本周産期・新生児医学会雑誌 Volume: 46(3) Pages: 813-817
  • NAID: 10026707522
  • Peer Reviewed
• [Presentation] 子宮体がんの発生とエストロゲン (2011)
  • Author(s): 塩沢丹里
  • Organizer: 第7回子宮体癌治療に関するシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-06-25
• [Presentation] 子宮体癌の発生とエストロゲン (2011)
  • Author(s): 塩沢丹里
  • Organizer: 第7回子宮体癌治療に関するシンポジウム
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-06-25
• [Presentation] 子宮体癌の発生とエストロゲン (2010)
  • Author(s): 塩沢丹里
  • Organizer: 第24回日本臨床細胞学会関東連合学術集会
  • Place of Presentation: 軽井沢
  • Year and Date: 2010-09-18
• [Presentation] エストロゲンと子宮内膜癌update (2010)
  • Author(s): 塩沢丹里
  • Organizer: 第122回近畿産婦人科学会オープニングレクチャー
  • Place of Presentation: 京都
  • Year and Date: 2010-06-19