The functional analysis of lipocalin2 and novel molecular targeted therapy for endometrial carcinoma

• Project/Area Number: 22591852
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: KASHIMA Hiroyasu 信州大学, 医学部, 助教 (70464089)
• Co-Investigator(Kenkyū-buntansha): MIYAMOTO Tsutomu 信州大学, 医学部附属病院, 講師 (70418721) ; SHIOZAWA Tanri 信州大学, 医学部, 教授 (20235493)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 癌 / 核酸 / タンパク質 / 発現制御 / 子宮内膜癌 / lipocalin2 / SLC22A17 / 生存能力 / 紫外線感受性 / シスプラチン感受性 / アポトーシス

Research Abstract

The expression of lipocalin2 (LCN2) was silenced using shRNA in HHUA, an endometrial carcinoma cell line over-expressing LCN2. The cell viability was significantly reduced and the apoptotic cells were significantly increased in this LCN2-silenced HHUA after ultraviolet (UV) irradiation or cisplatin (CDDP) treatment. The iron-chelating also reduced cell viability similar to LCN2-suppression. The expression of phosphorylated Akt was reduced in LCN2-silenced HHUA. These findings suggested that LCN2 enhanced cell survival via iron and Akt phosphorylation.

Research Products

• [Journal Article] Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells (2012)
  • Author(s): Mitsuhashi Y, Horiuchi A, Miyamoto T, Kashima H, Suzuki A, Shiozawa T
  • Journal Title: Histopathology Volume: 60 Pages: 826-37
  • Peer Reviewed
• [Journal Article] Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis (2012)
  • Author(s): Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T
  • Journal Title: Hum Pathol Volume: 43 Pages: 1964-72
  • 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 Pages: 1265-74
  • NAID: 120007107405
  • 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 resonance imaging 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, Kadoya M, Hashi A, Susumu N, Konishi I
  • Journal Title: Int J Gynecol Cancer Volume: 21 Pages: 1287-96
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma (2011)
  • Author(s): Miyamoto T, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T
  • Journal Title: Exp Mol Pathol. Volume: 91 Pages: 563-8
  • NAID: 120007107372
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of keratan sulfate: a possible diagnostic marker for 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 Pages: 1058-63
  • NAID: 120007107373
  • 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: Human Pathology Volume: 42 Pages: 1265-1274
  • NAID: 120007107405
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma (2011)
  • Author(s): Miyamoto T, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T
  • Journal Title: Experimental and molecular pathology Volume: 91 Pages: 563-568
  • NAID: 120007107372
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of keratan sulfate : a possible diagnostic marker for 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: Journal of clinical pathology Volume: 64 Pages: 1058-1063
  • NAID: 120007107373
  • Peer Reviewed
• [Journal Article] Laser-captured microdissection-microarray analysis of the genes involved in endo metrial carcinogenesis: stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance. (2011)
  • Author(s): Miyamoto T., et al.
  • Journal Title: Human Pathology Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of steroid receptor cofactors in ovarian endometriosis: involvement of down-regulated SRC-1 expression in the limited growth 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 Pages: 433-41
  • 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 Pages: 848-58
  • Peer Reviewed
• [Presentation] 早期卵巣癌におけるリンパ節郭清不要症例の抽出に Multidetector CT および MRI は有用か (2012)
  • Author(s): 宮本 強、橘 涼太、近藤沙織、 鹿島大靖、浅香志保、藤永康成、塩沢丹里
  • Organizer: 第123回関東連合産科婦人科学会学術集会
  • Place of Presentation: ワークショップ 東京
  • Year and Date: 2012-06-17
• [Presentation] Sirtuin1(SIRT1),a longevity gene,is over-expressed in endometrial carcinoma (2012)
  • Author(s): Asaka R,Miymamoto T,Suzuki A,IshikawaK,Yamada Y,Kobara H,Shiozawa T
  • Organizer: 14th International Gynecologic Cancer Society(IGCS)
  • Place of Presentation: Oral Vancouver Canada
• [Presentation] The expression of lipocalin2 in ovarian carcinoma and endometriosis. (2012)
  • Author(s): Yamada Y,Miyamoto T,Asaka R,Ishikawak,Kobara H,Suzuki A,Shiozawa T
  • Organizer: 14th International Gynecologic Cancer Society(IGCS)
  • Place of Presentation: Poster Vancouver Canada
• [Presentation] Lipocalin2 enhances the proliferation of endometrial carcinoma cells in nude mice (2012)
  • Author(s): Miyamoto T,Asaka R,Yamada Y,Ishikawa K,Kobara H,Suzuki A,Kashima H,Shiozawa T
  • Organizer: 14th International Gynecologic Cancer Society(IGCS)
  • Place of Presentation: Poster Vancouver Canada
• [Presentation] Lipocalin2 は子宮内膜症から発生する卵巣癌で高発現している (2012)
  • Author(s): 山田 靖、 宮本 強、浅香亮一、石川香織、小原久典、鈴木昭久、 鹿島大靖、 塩沢丹里
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ポスター 札幌
• [Presentation] Lipocalin2 はヌードマウスでの子宮内膜癌細胞の腫瘍増大を促進する (2012)
  • Author(s): 宮本 強、浅香亮一、山田 靖、石川香織、小原久典、鈴木昭久、 鹿島大靖、 塩沢丹里
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 口演 札幌
• [Presentation] 正常内膜および子宮内膜癌におけるSirtuin1(SIRT1)の発現と機能の検討 (2012)
  • Author(s): 浅香亮一、 宮本 強、石川香織、山田 靖、小原久典、鈴木昭久、塩沢丹里
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ポスター 札幌
• [Presentation] Lipocalin2 は紫外線照射後およびシスプラチン処理後の子宮内膜癌細胞の生存を促進する (2012)
  • Author(s): 宮本 強、浅香亮一、鈴木昭久、 鹿島大靖、塩沢丹里
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 一般講演 神戸
• [Presentation] 正常子宮内膜および子宮内膜癌における (2012)
  • Author(s): 浅香亮一、 宮本 強、鈴木昭久、 鹿島大靖、塩沢丹里
  • Organizer: sirtuin1 発現の検討
  • Place of Presentation: 一般講演 神戸
• [Presentation] Lipocalin2は紫外線照射後およびシスプラチン処理後の子宮内膜癌細胞の生存を促進する (2012)
  • Author(s): 宮本 強
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] Lipocalin2はヌードマウスでの子宮内膜癌細胞の腫瘍増大を促進する (2012)
  • Author(s): 宮本 強
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Lipocalin2は子宮内膜症から発生する卵巣癌で高発現している (2012)
  • Author(s): 山田 靖
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Lipocalin2 enhances the proliferation of endometrial carcinoma cells in nude mice (2012)
  • Author(s): Miyamoto T
  • Organizer: 14th International Gynecologic Cancer Society(IGCS)
  • Place of Presentation: Vancouver
• [Presentation] 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, Asaka R, Imanishi T, Kashima H, Shiozawa T
  • Organizer: 2nd Biennial Meeting of Asian Society of Gynecologic Oncology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2011-11-04
• [Presentation] 集学的癌治療により腫瘍随伴ネフローゼ症候群が寛解した婦人科癌の2例 (2011)
  • Author(s): 鹿島大靖, 他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-08-30
• [Presentation] 子宮内膜癌におけるlipocalin2受容体SLC22A17発現の検討 (2011)
  • Author(s): 宮本強, 浅香亮一, 鈴木昭久, 高津亜希子, 鹿島大靖, 塩沢丹里
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-08-29
• [Presentation] 子宮内膜癌発癌に関する基礎的研究、および婦人科悪性腫瘍手術の新たな展開 (2011)
  • Author(s): 宮本 強
  • Organizer: 松本市・塩筑合同産婦人科医会
  • Place of Presentation: 松本
  • Year and Date: 2011-01-19
• [Presentation] Immunohistochemical expression of Core2 β1-6 N-acetylglucosaminyl transferase 1 in the endometrial carcinoma;a novel potential prognostic factor. (2011)
  • Author(s): Asaka R,Miyamoto T,Suzuki A,Takatsu A, Kashima H,Nakayama J,Shiozawa T
  • Organizer: Asian Society of Gynecologic Oncology
  • Place of Presentation: Poster korea
• [Presentation] Lasr captured microdissection-microarray analysis of the genes innolved in endometrial carcinogenesis:stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria,and its functional relevance (2011)
  • Author(s): Miyamoto T,Asaka R,Imanishi T,Kashima H,Shiozawa T
  • Organizer: Asian Society of Gynecologic Oncology
  • Place of Presentation: Oral korea
• [Presentation] 子宮内膜癌の新規予後因子としての糖転移酵素 C2GnT1 発現 (2011)
  • Author(s): 浅香亮一、宮本 強、鈴木昭久、高津亜希子、鹿島大靖、中山 淳、塩沢丹里
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: ポスター 名古屋
• [Presentation] Lipocalin2は、紫外線照射に対する子宮内膜癌細胞の生存能力を上昇させる. (2011)
  • Author(s): 宮本 強、浅香亮一、鈴木昭久、高津亜希子、鹿島大靖、塩沢丹里
  • Organizer: Lipocalin2は、紫外線照射に対する子宮内膜癌細胞の生存能力を上昇させる.
  • Place of Presentation: ポスター 名古屋
• [Presentation] 子宮内膜癌における lipocalin2 受容体 SLC22A17 発現の検討 (2011)
  • Author(s): 宮本 強、浅香亮一、鈴木昭久、高津亜希子、鹿島大靖、塩沢丹里
  • Organizer: 第63回日本産科婦人科学会・総会・学術講演会
  • Place of Presentation: 大阪
• [Presentation] Lipocalin2は、紫外線照射に対する子宮内膜癌細胞の生存能力を上昇させる (2011)
  • Author(s): Miyamoto T, et al
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 子宮内膜腺上皮におけるケラタン硫酸およびC2GnT1発現とその診断への臨床応用 (2010)
  • Author(s): 宮本強、小原久典、浅香亮一、鹿島大靖, 他
  • Organizer: 第49回臨床細胞学会秋季大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-11-22
• [Presentation] Microarray analysis of the genes involved in endometrial carcinogenesis: up-regulation of lipocRlin9. in neoplastic endometria, and its functional relevance. (2010)
  • Author(s): Tsutomu Miyamoto, et al.
  • Organizer: 13th Biennial Meeting of the International Gynecologic Cancer Society (IGCS2010)
  • Place of Presentation: Prague, Czech
  • Year and Date: 2010-10-26
• [Presentation] LCN2R expression in endometrial carcinoma (2010)
  • Author(s): Tsutomu Miyamoto, et al.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 子宮内膜腺上皮におけるケラタン硫酸および C2GnT1 発現とその診断への応用 (2010)
  • Author(s): 宮本 強、石井恵子、小原久典、浅香亮一、高津亜希子、鈴木昭久、鹿島大靖、中山 淳、塩沢丹里
  • Organizer: 第49回日本臨床細胞学会秋期大会
  • Place of Presentation: ワークショップ 神戸
• [Presentation] Pre-operative diagnosis and the management of minimal deviation adenocarcinoma(MDA)and lobular endocervical glandular hyperplasia(LEGH):a multi-center,retrospective study (2010)
  • Author(s): Takatsu A,Fuseya C, Miyamoto T,Horiuchi A, Shiozawa T
  • Organizer: International Gynecologic Cancer Society(IGCS 2010)
  • Place of Presentation: poster Praha Ceska republika
• [Presentation] Microarray analysis of the genes involved in endometrial carcinogenesis:up-regulation of lipocalin2 in neoplastic endometria,and its functional relevance (2010)
  • Author(s): Miyamoto T,Kashima H, Suzuki A,Kikuchi N,Takatsu A,Konishi I, Seki N,Shiozawa T
  • Organizer: International Gynecologic Cancer Society(IGCS 2010)
  • Place of Presentation: Oral presentation Praha Ceska republika
• [Presentation] 子宮内膜癌における lipocalin2 受容体発現 (2010)
  • Author(s): 宮本 強、浅香亮一、鈴木昭久、高津亜希子、堀内晶子、塩沢丹里
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 一般講演 大阪