Matabolome and Autophagy in Ovarian Clear Cell Carcinoma

• Project/Area Number: 24791700
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: YAMAGUCHI Ken 京都大学, 医学(系)研究科(研究院), 助教 (20378772)
• Project Period (FY): 2012-04-01 – 2014-03-31 (Estimated)
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 卵巣明細胞腺癌 / 代謝 / アミノ酸トランスポーター / グルタチオン / 酸化ストレス

Research Abstract

To elucidate HNF1B induces metabolic activities in ovarian clear cell carcinoma (CCC) cells, we assessed comprehensive metabolomic analyses using CE-TOFMS(capillary electrophoresis time-of-flight mass spectrometry) between HNF1B knockdown CCC cell line and control cell line. HNF1B changed glucose metabolism and caused aerobic glucolysis that was well known as the Warburg effect in CCC cells. HNF1B also increased intracellular glutathione levels through a cystine transporter, SLC3A1, expression. Intracellular glutathione levels and reactive oxygen species (ROS) were significantly decreased in SLC3A1 knockdown cells.
These results suggest that HNF1B contribute to resistance to anti-oxidative stress through the Warburg effect and intracellular glutathione in ovarian clear cell carcinoma.

Research Products

• [Journal Article] Epigenetic determinants of ovarian clear cell carcinoma biology (2014)
  • Author(s): Yamaguchi K, Huang Z, Matsumura N, Mandai M, Okamoto T, Baba T, Konishi I, Berchuck A, Murphy SK
  • Journal Title: Int J Cancer Volume: 135(3) Pages: 585-97
  • DOI: 10.1002/ijc.28701
• [Journal Article] Two cases of recurrent ovarian clear cell carcinoma treated with sorafenib. (2014)
  • Author(s): Koshiyama M, Matsumura N, Baba T, Yamaguchi K, Yoshioka Y, Konishi I.
  • Journal Title: Cancer Biol Ther. Volume: 15 Pages: 22-5
  • DOI: 10.4161/cbt.26608.
  • Peer Reviewed
• [Journal Article] Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma (2013)
  • Author(s): Okamoto T, Mandai M, Matsumura N, Yamaguchi K, Kondoh H, Amano Y, Baba T, Hamanishi J, Abiko K, Kosaka K, Murphy SK, Mori S, Konishi I
  • Journal Title: Mol Carcinog Volume: (Epub ahead of print)
  • DOI: 10.1002/mc.22072
• [Journal Article] 遺伝子発現マイクロアレイに基づく卵巣癌の予後予測 (2013)
  • Author(s): 松村謙臣, 山口建, 小西郁生
  • Journal Title: 予後予測因子の新知見PROGRESS in Ovarian Cancer Management Volume: Vol.1 No.1 Pages: 39-43
• [Journal Article] 次世代の婦人科がん治療を展望する「ゲノムワイドな解析に基づく卵巣癌の新規治療法の開発」 (2013)
  • Author(s): 松村謙臣, 山口建, 万代昌紀, 小西郁生
  • Journal Title: 産婦人科の実際 Volume: Vol.62, No.3 Pages: 307-313
• [Journal Article] Epigenetic determinants of ovarian clear cell carcinoma biology. (2013)
  • Author(s): Yamaguchi K, Huang Z, Matsumura N, Mandai M, Okamoto T, Baba T, Konishi I, Berchuck A, Murphy SK.
  • Journal Title: Int J Cancer. Volume: - Pages: -
  • DOI: 10.1002/ijc.28701
  • Peer Reviewed
• [Journal Article] A novel diagnostic criterion for lymph node metastasis in cervical cancer using multi-detector computed tomography. (2013)
  • Author(s): Yamanoi K, Matsumura N, Kido A, Baba T, Hamanishi J, Yamaguchi K, Yoshioka Y, Abou Taleb H, Togashi K, Konishi I.
  • Journal Title: Gynecol Oncol. Volume: 131 Pages: 707-7
  • DOI: 10.1016/j.ygyno.2013.10.014.
  • Peer Reviewed
• [Journal Article] Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma. (2013)
  • Author(s): Okamoto T, Mandai M, Matsumura N, Yamaguchi K, Kondoh H, Amano Y, Baba T, Hamanishi J, Abiko K, Kosaka K, Murphy SK, Mori S, Konishi I.
  • Journal Title: Mol Carcinog Volume: - Pages: -
  • DOI: 10.1002/mc.22072.
  • Peer Reviewed
• [Journal Article] Ileal perforation and massive intestinal haemorrhage from endometriosis in pregnancy: case report and literature review. (2013)
  • Author(s): Nishikawa A, Kondoh E, Hamanishi J, Yamaguchi K, Ueda A, Sato Y, Konishi I.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: 170 Pages: 20-4
  • DOI: 10.1016/j.ejogrb.2013.04.018.
  • Peer Reviewed
• [Journal Article] Utilization of genomic signatures to identify high-efficacy candidate drugs for chemorefractory endometrial cancers. (2013)
  • Author(s): Kharma B, Baba T, Mandai M, Matsumura N, Murphy SK, Kang HS, Yamanoi K, Hamanishi J, Yamaguchi K, Yoshioka Y, Konishi I.
  • Journal Title: Int J Cancer. Volume: 133 Pages: 2234-44
  • DOI: 10.1002/ijc.28220.
  • Peer Reviewed
• [Journal Article] PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction. (2013)
  • Author(s): Abiko K, Mandai M, Hamanishi J, Yoshioka Y, Matsumura N, Baba T, Yamaguchi K, Murakami R, Yamamoto A, Kharma B, Kosaka K, Konishi I.
  • Journal Title: Clin Cancer Res. Volume: 19 Pages: 1363-74
  • DOI: 10.1158/1078-0432.CCR-12-2199.
  • Peer Reviewed
• [Journal Article] Utilization of genomic signatures to identify high efficacy candidate drugs for chemo-refractory endometrial cancers. (2013)
  • Author(s): Kharma B, Baba T, Mandai M, Matsumura N, Murphy SK, Kang HS, Yamanoi K, Hamanishi J, Yamaguchi K, Yoshioka Y, Konishi I.
  • Journal Title: Int J Cancer. Volume: in press Pages: in press
  • DOI: 10.1002/ijc.28220
  • Peer Reviewed
• [Journal Article] 卵巣明細胞腺癌における特異的遺伝子発現と分子標的治療への展開 (2012)
  • Author(s): 万代昌紀, 山口建, 松村謙臣, 岡本尊子, 天野泰彰, 馬場長, 小西郁生
  • Journal Title: 産科と婦人科 Volume: 79 Pages: 1279-1284
• [Journal Article] Expression pattern of Galectin 4 in rat placentation. (2012)
  • Author(s): Arikawa T, Simamura E, Shimada H, Nishi N, Tatsuno T, Ishigaki Y, Tomosugi N, Yamashiro C, Hata T, Takegami T, Mogami H, Yamaguchi K, Nakamura T, Otani H, Hatta T, Shoji H.
  • Journal Title: Placenta Volume: 33 Pages: 885-7
  • DOI: 10.1016/j.placenta.2012.07.013
  • Peer Reviewed
• [Journal Article] Clinical management of ovarian endometriotic cyst (chocolate cyst)-diagnosis, medical treatment and minimal invasive surgery. (2012)
  • Author(s): Mandai M, Suzuki A, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Yoshioka Y, Kosaka K, Konishi I
  • Journal Title: Curr Obstet Gynecol Rep. Volume: 1 Pages: 16-24
  • DOI: 0.1007/s13669-011-0002-3
  • Peer Reviewed
• [Journal Article] 卵巣明細胞腺癌における特異的遺伝子発現と分子標的治療への展開 (2012)
  • Author(s): 万代昌紀、山口建、松村謙臣、岡本尊子、天野泰彰、馬場長、小西郁生
  • Journal Title: 産科と婦人科 Volume: 79 Pages: 1279-84
• [Presentation] Selection of drugs against ovarian cancer based on gene expression profile (2013)
  • Author(s): Noriomi Matsumura, Ryusuke Murakami, Masafumi Koshiyama, Tsukasa Baba, Junzo Hamanishi, Ken Yamaguchi, Kaoru Abiko, Yumiko Yoshioka, Ikuo Konishi
  • Organizer: The 3rd Asian Society of Gynecologic Oncology meeting
  • Place of Presentation: ウェスティン都ホテル(京都)
  • Year and Date: 20131213-20131215
• [Presentation] SWI/SNF complex is a novel prognostic factor in clear cell carcinoma (CCC) of the ovary (2013)
  • Author(s): Abou-Taleb, Ken Yamaguchi, Noriomi Matsumura, Yasuaki Amano, Koji Yamanoi, Ryusuke Murakami, Tsukasa Baba, Yumiko Yoshioka, Junzo Hamanishi, Masaki Mandai, Ikuo Konishi
  • Organizer: The 3rd Asian Society of Gynecologic Oncology meeting
  • Place of Presentation: ウェスティン都ホテル(京都)
  • Year and Date: 20131213-20131215
• [Presentation] 卵巣明細胞腺癌における酸化ストレス遺伝子群のエピジェネティクな変化 (2013)
  • Author(s): 山口 建、松村謙臣、万代昌紀、天野泰彰、安彦 郁、濱西潤三、吉岡弓子、馬場 長、越山雅文、Susan K Murphy、小西郁生
  • Organizer: 京都婦人科腫瘍フォーラム
  • Place of Presentation: ウェスティン都ホテル(京都)
  • Year and Date: 20131011-20131011
  • Invited
• [Presentation] 転写因子HNF1βは、腫瘍代謝を誘導することで、卵巣明細胞腺癌の酸化ストレス耐性に寄与している／HNF1β contributes to the ROS resistance of ovarian clear cell carcinoma cells, modifying its metabolic process (2013)
  • Author(s): 天野 泰彰、山口 建、万代 昌紀、松村 謙臣、馬場 長、濱西 潤三、吉岡 弓子、安彦 郁、奈倉 道和、Abou-Taleb Hisham、村上 隆介、山ノ井 康二、小西 郁生
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 20131003-20131005
• [Presentation] 転写因子 HNF1βは, 腫瘍代謝を誘導することで, 卵巣明細胞腺癌の酸化ストレス耐性に寄与している/HNF1β contributes to the ROS resistance of ovarian clear cell carcinoma cells, modifying its metabolic process (2013)
  • Author(s): 天野 泰彰, 山口 建, 万代 昌紀, 松村 謙臣, 馬場 長, 濱西 潤三, 吉岡 弓子, 安彦 郁, 奈倉 道和, Abou-Taleb Hisham, 村上 隆介, 山ノ井 康二, 小西 郁生
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市, パシフィコ横浜
  • Year and Date: 20131003-05
• [Presentation] HNF-1β confers resistance to oxidative stress of ovarian clear cell carcinoma (2013)
  • Author(s): Yasuaki Amano, Ken Yamaguchi, Masaki Mandai, Noriomi Matsumura, Junzo Hamanishi, Tsukasa Baba, Koji Yamanoi, Susan K Murphy, Ikuo Konishi
  • Organizer: An AACR Special Coference on Advances in Ovarian Cancer Research
  • Place of Presentation: フロリダ州マイアミ, J.W. Marriott Marquis Miami
  • Year and Date: 20130918-21
• [Presentation] HNF-1β confers resistance to oxidative stress of ovarian clear cell carcinoma. (2013)
  • Author(s): Yasuaki Amano, Ken Yamaguchi, Masaki Mandai, Noriomi Matsumura, Junzo Hamanishi, Tsukasa Baba, Koji Yamanoi, Susan K Murphy, Ikuo Konishi
  • Organizer: An AACR Special Coference on Advances in Ovarian Cancer Research
  • Place of Presentation: アメリカ、フロリダ州、マイアミ
  • Year and Date: 20130908-20130912
• [Presentation] 転写因子 HNF1βは, アミノ酸輸送体rBAT を介して, 卵巣明細胞腺癌の酸化ストレス耐性に寄与する (2013)
  • Author(s): 天野泰彰, 山口建, 馬場長, 濱西潤三, 吉岡弓子, 安彦郁, 奈倉道和, 村上隆介, 山ノ井康二, 松村謙臣, 小西郁生
  • Organizer: 第54回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京, ホテルグランパシフィック LE DAIBA
  • Year and Date: 20130719-21
• [Presentation] 卵巣明細胞腺癌において, 転写因子HNF1βはアミノ酸輸送体を介して腫瘍性代謝を制御し, 酸化ストレス耐性に寄与する (2013)
  • Author(s): 天野泰彰, 万代昌紀, 山口建, 松村謙臣, 馬場長, 濱西潤三, 吉岡弓子, 安彦郁, 奈倉道和, 村上隆介, 山ノ井康二, 小西郁生
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌市, ロイトン札幌/ホテル札幌芸文館/札幌プリンスホテル/札幌市教育文化会館
  • Year and Date: 20130510-12
• [Presentation] 子宮内膜症の発がんと酸化ストレス (2012)
  • Author(s): 万代昌紀、山口建、松村謙臣、馬場長、岡本尊子、天野泰彰、濱西潤三、Susan K. Murphy、小西郁生
  • Organizer: 第17回日本生殖内分泌学会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)
  • Year and Date: 20121208-20121208
• [Presentation] 公募研究報告「発現マイクロアレイ解析に基づく卵巣明細胞腺癌(OCCC)の病態の解明」 (2012)
  • Author(s): 松村謙臣、万代昌紀、山口建、岡本尊子、天野泰彰、Hisham Abou-Taleb、馬場長、濱西潤三、吉岡弓子、小阪謙三、小西郁生
  • Organizer: 第53回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)
  • Year and Date: 20121123-20121124
  • Invited
• [Presentation] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-------A potential therapeutic target (2012)
  • Author(s): Peng Jin, Yumiko Yoshioka, Masaki Mandai, Ken Yamaguchi, Noriomi Matsumura, Kaoru Abiko, Budiman Kharma, Tsukasa Baba, Junzo Hamanishi, Kenzo Kosaka and Ikuo Konishi
  • Organizer: the FIRC Institute of Molecular Oncology Foundation - Kyoto University (IFOM-KU) Joint Symposium 2012
  • Place of Presentation: イリノイ州 シカゴ
  • Year and Date: 20121024-20121029
• [Presentation] Tumor-associated Lymphocytes Attenuate Tumor Immunity to Promote Progression of Serous Endometrial Cancer via STAT1 pathway (2012)
  • Author(s): Budiman Kharma, Tsukasa Baba, Hyun Sook Kang, Masaki Mandai, Junzo Hamanishi, Yumiko Yoshioka, Noriomi Matsumura, Ken Yamaguchi and Ikuo Konishi
  • Organizer: the 14th Biennial Meeting of the International Gynecologic Cancer Society (IGCS)
  • Place of Presentation: テキサス州 オースチン
  • Year and Date: 20121013-20121016
• [Presentation] CORRELATION OF GENE EXPRESSION PROFILE WITH HISTOLOGICAL FEATURE IN OVARIAN HIGH-GRADE SEROUS CARCINOMA (2012)
  • Author(s): Murakami R, Masumura N, Yoshihara K, Yamanoi K, Peng J, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba, T Mandai M, Tanaka K and Konishi I
  • Organizer: the 14th Biennial Meeting of the International Gynecologic Cancer Society (IGCS)
  • Place of Presentation: ブリティッシュコロンビア州 バンクーバー
  • Year and Date: 20121013-20121016
• [Presentation] 卵巣明細胞腺癌における ROS 耐性には, 転写因子 HNF1βの発現が関与している (2012)
  • Author(s): 天野泰彰, 万代昌紀, 山口建, 松村謙臣, 馬場長, 濱西潤三, 吉岡弓子, 安彦郁, 奈倉道和, 小西郁生
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市, ロイトン札幌/さっぽろ芸文館/札幌市教育文化会館
  • Year and Date: 20120919-21
• [Presentation] 卵巣明細胞腺癌の酸化ストレス耐性; in vivo における検討 (2012)
  • Author(s): 天野泰彰, 万代昌紀, 山口建, 小阪謙三, 松村謙臣, 馬場長, 濱西潤三, 吉岡弓子, 安彦郁, 奈倉道和, 小西郁生
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京, 東京グランドプリンスホテル新高輪
  • Year and Date: 20120719-21
• [Presentation] 卵巣明細胞腺癌に特異的に発現するHNF1βは, ROS 耐性に関与している (2012)
  • Author(s): 天野泰彰, 万代昌紀, 山口建, 小阪謙三, 松村謙臣, 馬場長, 濱西潤三, 吉岡弓子, 安彦郁, Hisham Ahed el-sayed abou-taleb, 岡本尊子, 小西郁生
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸市, 神戸ポートピアホテル/神戸国際展示場
  • Year and Date: 20120413-15
• [Book] PROGRESS in Ovarian Cancer Management (2013)
  • Author(s): 松村謙臣、山口建、小西郁生
  • Total Pages: 39-43
  • Publisher: メディカルビュー社
• [Book] 産婦人科の実際 (2013)
  • Author(s): 松村謙臣、山口建、万代昌紀、小西郁生
  • Total Pages: 307-313
  • Publisher: 金原出版