Estrogen-related receptor alpha as a potential target for endometrial cancer

• Project/Area Number: 15K10726
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Mori Taisuke 京都府立医科大学, 医学(系)研究科(研究院), 講師 (00569824)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 子宮体癌 / ホルモン依存性腫瘍 / エストロゲン受容体 / ホルモン療法

Outline of Final Research Achievements

The elevated levels of ERRa was associated with advanced clinical stages and serous histological type. ERRa demonstrated negative prognostic significance. Knockdown of ERRa suppressed angiogenesis via VEGF, inhibited cell proliferation and induced cell cycle arrest at the mitotic phase and caspase-3 dependent apoptosis. A significant reduction of tumor growth and angiogenesis was observed in xenografts with ERRa knockdown. We propose that ERRa can serve as a novel target for molecular therapy of endometrial cancer.

Research Products

• [Journal Article] Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis. (2018)
  • Author(s): Takekuma M, Shimokawa M, Nishio S, Omi H, Tabata T, Takei Y, Nasu K, Takahashi Y, Toyota S, Ichikawa Y, Arakawa A, Ito F, Tsubamoto H, Mori T, Hirashima Y, Ito K.
  • Journal Title: Cancer Sci Volume: 25 Issue: 5 Pages: 1602-1608
  • DOI: 10.1111/cas.13577
  • Peer Reviewed / Open Access
• [Journal Article] Long-term survival with bevacizumab in heavily pretreated and platinum-resistant mucinous ovarian cancer: A case report (2017)
  • Author(s): Tarumi Yosuke、Mori Taisuke、Matsushima Hiroshi、Kokabu Tetsuya、Tsuchiya Hiroshi、Kitawaki Jo
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 44 Issue: 2 Pages: 347-351
  • DOI: 10.1111/jog.13496
  • Peer Reviewed / Open Access
• [Journal Article] Exacerbation of Endometriosis Due To Regulatory T-Cell Dysfunction. (2017)
  • Author(s): Tanaka Y, Mori T, Ito F, Koshiba A, Takaoka O, Kataoka H, Maeda E, Okimura H, Mori T, Kitawaki J.
  • Journal Title: J Clin Endocrinol Metab Volume: 102 Pages: 3206-3217
  • Peer Reviewed / Open Access
• [Journal Article] Current status of tertiary debulking surgery and prognosis after secondary debulking surgery for recurrent mullerian epithelial cancer in Japan: a retrospective analysis of 164 patients (KCOG-G1402). (2017)
  • Author(s): Hirakawa T, Minaguchi T, Itani Y, Kasamatsu Y, Murase S, Sakurada S, Nagano H, Takehara K, Tsuruta T, Arakawa A, Kawano K, Tsubamoto H, Ushiwaka T, Mori T, Iwai K, Saito M, Morisawa H, Saito F, Yoshida K, Kaneuchi M, Sato H, Ito K, Nasu K.
  • Journal Title: World J Surg Oncol. Volume: 15 Pages: 132-132
  • Peer Reviewed / Open Access
• [Journal Article] Preparation of a novel antiserum to aromatase with high affinity and specificity: its clinicopathological significance on breast cancer tissue. (2017)
  • Author(s): Naoki Kanomata, Shiro Matsuura, Junichi Kurebayashi, Taisuke Mori, Junya Nakamura, Jo Kitawaki, Takuya Moriya
  • Journal Title: PLoS One Volume: 12 Issue: 5 Pages: e0177439-e0177439
  • DOI: 10.1371/journal.pone.0177439
  • Peer Reviewed / Open Access
• [Journal Article] Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice (2017)
  • Author(s): Amano A, Kondo Y, Noda Y, Ohta M, Kawanishi N, Machida S, Mitsuhashi K, Senmaru T, Fukui M, Takaoka O, Mori T, Kitawaki J, Ono M, Saibara T, Obayashi H, Ishigami A.
  • Journal Title: Arch Biochem Biophys Volume: - Pages: 47-58
  • DOI: 10.1016/j.abb.2017.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Increased ipsilateral uterine artery vascular resistance in women with ovarian endometrioma (2017)
  • Author(s): Waratani Miyoko、Mori Taisuke、Ito Fumitake、Tanaka Yukiko、Koshiba Akemi、Takahata Akiko、Kitawaki Jo
  • Journal Title: Journal of Obstetrics and Gynaecology Research Volume: 43 Issue: 4 Pages: 736-743
  • DOI: 10.1111/jog.13266
  • Peer Reviewed / Open Access
• [Journal Article] Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer. (2016)
  • Author(s): Matsushima H, Mori T, Ito F, Yamamoto T, Akiyama M, Kokabu T, Yoriki K, Umemura S, Akashi K, Kitawaki J.
  • Journal Title: Oncotarget. Volume: 3 Issue: 23 Pages: 3-3
  • DOI: 10.18632/oncotarget.9151
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of low-dose combined drospirenone-ethinylestradiol on perimenstrual symptoms experienced by women with endometriosis (2016)
  • Author(s): Tanaka Y, Mori T, Ito F, Koshiba A, Kusuki I, Kitawaki J
  • Journal Title: Int J Gynaecol Obstet Volume: 135 Issue: 2 Pages: 135-139
  • DOI: 10.1016/j.ijgo.2016.05.004
  • Peer Reviewed / Open Access
• [Journal Article] Apocrine Adenocarcinoma of the Vulva: A Case Report and Review of the Literature. (2016)
  • Author(s): Aoyama K, Matsushima H, Sawada M, Mori T, Yasukawa S, Kitawaki J.
  • Journal Title: Case Rep Obstet Gynecol Volume: 2016 Pages: 1712404-1712404
  • DOI: 10.1155/2016/1712404
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enlarged uterine corpus volume in women with endometriosis: Assessment using three-dimensional reconstruction of pelvic magnetic resonance images. (2016)
  • Author(s): Koshiba A, Mori T, Ito F, Tanaka Y, Takaoka O, Takahata A, Kitawaki J.
  • Journal Title: J Obstet Gynaecol Res Volume: 43 Issue: 1 Pages: 157-163
  • DOI: 10.1111/jog.13153
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Primary osteosarcoma of the uterine corpus: A case report. (2016)
  • Author(s): Tsukasaki N, Mori T, Yasukawa S, Konishi E, Kokabu T, Kitawaki J.
  • Journal Title: J Obstet Gynaecol Res. Volume: 42 Issue: 11 Pages: 1604-1608
  • DOI: 10.1111/jog.13079
• [Journal Article] Effects of drospirenone on adhesion molecule expression and monocyte adherence in human endothelial cells. (2016)
  • Author(s): Ito F, Mori T, Takaoka O, Tanaka Y, Koshiba A, Tatsumi H, Iwasa K, Kitawaki J.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 201 Pages: 113-117
  • DOI: 10.1016/j.ejogrb.2016.03.044
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of AF-6/afadin induces cell invasion, suppresses the formation of glandular structures and might be a predictive marker of resistance to chemotherapy in endometrial cancer. (2015)
  • Author(s): Yamamoto T, Mori T, Sawada M, Matsuhima H, Ito F, Akiyama M, Kitawaki J
  • Journal Title: BMC Cancer Volume: in press Issue: 1 Pages: 275-284
  • DOI: 10.1186/s12885-015-1286-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes (2015)
  • Author(s): Ohta, Mitsuhiro; Fujinami, Aya; Kobayashi, Norihiro; Amano, Akiko; Ishigami, Akihito; Tokuda, Harukuni; Suzuki, Nobutaka; Ito, Fumitake; Mori, Taisuke; Sawada, Morio;
  • Journal Title: Nutrition Research Volume: 35(7) Issue: 7 Pages: 618-625
  • DOI: 10.1016/j.nutres.2015.05.010
  • Peer Reviewed
• [Journal Article] Endometrioid adenocarcinoma arising from deep infiltrating endometriosis involving the bladder: A case report and review of the literature. (2015)
  • Author(s): Tarumi Y, Mori T, Kusuki I, Ito F, Kitawaki J.
  • Journal Title: Gynecol Oncol Rep Volume: 13 Pages: 68-70
  • DOI: 10.1016/j.gore.2015.07.003
  • Peer Reviewed
• [Presentation] Peroxisome-Proliferator-Activated Receptor-g Coactivator-1a (PGC-1a) Enhances Local Estrogen Biosynthesis by Stimulating Aromatase Activity in Endometriosis (2017)
  • Author(s): Taisuke Mori
  • Organizer: 3th SEUD Singapole
  • Int'l Joint Research / Invited
• [Presentation] エストロゲン生合成経路からみた子宮内膜症の病態解明と新たな治療戦略 (2017)
  • Author(s): 森 泰輔
  • Organizer: 日本内分泌学会シンポジウム
  • Invited
• [Presentation] Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer. (2016)
  • Author(s): 松島洋
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21