Roles of steroid and xenobiotic receptor (SXR) on ER-mediated transcription in breast cancer cells

2011 Fiscal Year Final Research Report

• Project/Area Number: 21791242
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Gunma University
• Principal Investigator: ROKUTANDA Nana 群馬大学, 医学部, 助教 (50420097)
• Project Period (FY): 2009 – 2011
• Keywords: 癌 / 核内受容体 / 外科

Research Abstract

The estrogen receptor (ER) is a key regulator of proliferation and differentiation in breast cancer cells. Steroid and xenobiotic receptor (SXR) is highly expressed in the liver and small intestine and regulates the expression of cytochrome P450 monooxygenase 3A4 (CYP3A4) and P-glycoprotein (P-gp) that is encoded by multidrug resistance 1 (MDR1) gene. SXR is also expressed in normal and neoplastic breast tissue. In the present study, the effect of steroid and xenobiotic receptor (SXR) on 17.-estradiol (E)-induced 2 transcription through ER. was studied. SXR augmented ER-mediated transcription in the presence of E in MCF-7 breast cancer-derived cells and CV-1 fibroblast-derived cells. SXR did not directly bind to ER. or ERE 2in vitro, indicating that SXR may affect ER-mediated transcription by altering cofactor biding to ER. Although SXR did not alter the binding between ER. and p300/CBP interacting protein (p/CIP), it decreased the binding of a specific corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT) to liganded ER. as assessed by mammalian two-hybrid, GST pull down, immunoprecipiation and newly developed Liquid Chemiluminescent DNA Pull Down Assays. These results indicate that SXR augmented ER-mediated transcription by dissociating SMRT from ER. Thus, the expression of SXR in breast cancer cells may alter the ER signaling, which may play crucial role for growth and differentiation of breast cancer cells. We performed realtime quantitative RT-PCR studies using SXR promoter. The expression of SXR mRNA was increased in those cases ER positive, PgR positive, HER2 negative, without node metastasis, and low grade.

Research Products

• [Journal Article] 乳癌におけるsteroid and xenobiotic receptor(SXR)の発現とERの相互作用について (2011)
  • Author(s): 六反田奈和, 堀口淳, 岩崎俊晴, 鯉渕幸生, 高他大輔, 長岡りん, 小田原宏樹, 時庭英彰, 戸塚勝理, 竹吉泉, 鯉渕典之
  • Journal Title: 乳癌基礎研究 Volume: 20 Pages: 7-10
• [Journal Article] 補助化学療法後の卵巣機能の変化と閉経状況 (2010)
  • Author(s): 六反田奈和, 鯉淵幸生, 堀口淳
  • Journal Title: 乳癌の臨床 Volume: 25(1) Pages: 23-29
  • Peer Reviewed
• [Journal Article] Isolated retromammary lymph node metastasis of breast cancer without axillary lymph node involvement : A case report with false negative sentinel lymph node biopsy、 (2009)
  • Author(s): Nana Rokutand, Jun Horiguchi, Koibuchi, Rin Nagaoka, Ayako Sato, Hiroki Odawara, Hideaki Tokiniwa, Yuichi Iino, Junko Hirato, Izumi Takeyoshi
  • Journal Title: Breast cancer Volume: 16 Pages: 162-165
  • Peer Reviewed
• [Presentation] Comparison of HER-2 and Hormone Receptor Expression in Primary Breast Cancers and Metastases (2012)
  • Author(s): Nana Rokutanda, Jun Horiguchi, Mami Kikuchi, Daisuke Takata, Rin Nagaoka, Ayako Sato, Hiroki Odawara, Hideaki Tokiniwa, Katsunori Tozuka, Izumi Takeyoshi
  • Organizer: 8th European Breast Cancer Conference
  • Place of Presentation: Vienn Austria
  • Year and Date: 2012-03-22
• [Presentation] Comparative analysis of hormone receptor status and HER-2 expression between primary and recurrent breast cancer (2011)
  • Author(s): Nana Rokutanda, Jun Horiguchi, Mami Kikuchi, Daisuke Takata, Rin Nagaoka, Ayako Sato, Hiroki Odawara, Hideaki Tokiniwa, Katsunori Tozuka, Izumi Takeyoshi
  • Organizer: Global Breast Cancer Conference with the 8th Biennial Meeting of the Asian Breast Cancer Society
  • Place of Presentation: 韓国
  • Year and Date: 2011-10-07
• [Presentation] 乳癌再発症例における、原発巣と転移再発巣のホルモン感受性およびHER2発現状況の比較検討 (2011)
  • Author(s): 六反田奈和, 堀口淳, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 時庭英彰, 戸塚勝理, 高井良樹, 小山徹也, 竹吉泉
  • Organizer: 第19回日本乳癌学会学術総
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-03
• [Presentation] 1腺のみ巨大に腫大した続発性副甲状腺機能亢進症の1手術例 (2011)
  • Author(s): 六反田奈和, 堀口淳, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 時庭英彰, 戸塚勝理, 小山徹也, 竹吉泉
  • Organizer: 第23回日本内分泌外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-08
• [Presentation] 早期乳癌における術前腋窩リンパ節の評価の検討 (2011)
  • Author(s): 六反田奈和, 堀口淳, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 小山徹也, 竹吉泉
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 紙上発表
  • Year and Date: 2011-05-25
• [Presentation] 異時両側乳癌の発見契機と画像所見～対側乳癌早期発見のための方法の検討～ (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生^*, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 竹吉泉
  • Organizer: 第72回日本臨床外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-11-21
• [Presentation] マンモグラフィで広範なdistortionを呈したcomplex sclerosing lesionを伴う乳癌症例の検討 (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 小山徹也, 竹吉泉
  • Organizer: 第20回日本乳癌検診学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-11-19
• [Presentation] 基礎疾患を有する患者の悪性腫瘍スクリーニングFDG-PETで発見された甲状腺癌の検討 (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 加藤隆二, 竹吉泉
  • Organizer: 第43回甲状腺外科学会総会
  • Place of Presentation: 倉敷
  • Year and Date: 2010-10-14
• [Presentation] 乳癌におけるsteroid and xenobiotic receptor(SXR)の発現とERとの相互作用について (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 加藤隆二, 竹吉泉
  • Organizer: 第20回乳癌基礎研究会
  • Place of Presentation: 宮崎
  • Year and Date: 2010-07-17
• [Presentation] 非浸潤性乳管癌に対する乳房温存術の治療成績 (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 高他大輔, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 加藤隆二, 飯野佑一, 竹吉泉
  • Organizer: 第18回日本乳癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-24
• [Presentation] Cushing症候群を呈した副腎Black adenomaの1例 (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 加藤隆二, 小山徹也, 竹吉泉
  • Organizer: 第22回日本内分泌外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-06-12
• [Presentation] 閉経前乳癌の化学療法後の内分泌環境の変化と内分泌療法の選択について (2010)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 黒住献, 飯野佑一, 竹吉泉
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] Chemotherapy-induced amenorrhea and adjuvant endocrine therapy for premenopausal women with early breast cancer (2010)
  • Author(s): Nana Rokutanda, Jun Horiguchi, Yukio Koibuchi, Mami Kikuchi, Rin Nagaoka, Ayako Sato, Hiroki Odawara, Hideaki Tokiniwa, Yuichi Iino, Izumi Takeyoshi
  • Organizer: 7th European Breast Cancer Conference
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-03-25
• [Presentation] 乳癌術後患者の乳癌検診方法について、異時両側乳癌症例における検討 (2009)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 黒住献, 飯野佑一, 竹吉泉
  • Organizer: 第19回日本乳癌検診学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-11-05
• [Presentation] 甲状腺epithelioid angiosarcomaの一例 (2009)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 小山徹也, 平戸純子, 宮永朋実, 飯野佑一, 竹吉泉
  • Organizer: 第42回甲状腺外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-10-15
• [Presentation] Predicting axillary lymphnode involvement in breast cancer patients by ultrasonography and computed tomography (2009)
  • Author(s): Nana Rokutanda, Jun Horiguchi, Koibuchi, Mami Kikuchi, Rin Nagaoka, Ayako Sato, Hiroki Odawara, Hideaki Tokiniwa, Katunori Totuka, Yuichi Iino, Izumi Takeyoshi
  • Organizer: Global Breast Cancer Conference
  • Place of Presentation: 韓国
  • Year and Date: 2009-10-08
• [Presentation] 化学療法による卵巣機能の変化と閉経状況の判定およびその後の内分泌療法について (2009)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 樋口徹, 内田紗弥香, 飯野佑一, 竹吉泉
  • Organizer: 第17回日本乳癌学会学術総会
  • Place of Presentation: 日、東京
  • Year and Date: 2009-07-03
• [Presentation] Cushing症候群を呈したmyelolipomatous metaplasiaを伴った副腎Black adenomaの1例 (2009)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 菊地麻美, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 戸塚勝理, 飯野佑一, 平戸純子, 小山徹也, 竹吉泉
  • Organizer: 第21回日本内分泌外科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2009-05-29
• [Presentation] 非浸潤性乳管癌(DCIS)に対する乳房温存術(BCS)による局所コントロールの検討 (2009)
  • Author(s): 六反田奈和, 堀口淳, 鯉淵幸生, 長岡りん, 佐藤亜矢子, 小田原宏樹, 時庭英彰, 樋口徹, 菊地麻美, 飯野佑一, 竹吉泉
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-02