mechanism of drug resistance in breast cancer : the correlation between steroid and xenobiotic receptor (SXR) and UDP-glucuronosyltransferase (UGT)

2009 Fiscal Year Final Research Report

• Project/Area Number: 19790912
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Gunma University
• Principal Investigator: ODAWARA Hiroki Gunma University, 医学部, 医員 (10420134)
• Project Period (FY): 2007 – 2009
• Keywords: 乳癌 / 薬物代謝 / UGT / SXR / エストロゲン

Research Abstract

Steroid and xenobiotic receptor (SXR) is ligand-activated transcription factor, which is a member of the nuclear hormone receptor superfamily. We have reported that SXR activated the expression of CYP3A4 and MDR-I, playing a part of phase I stage in drug metabolism, in breast cancer cells lines. Conjugation is the phase II stage of drug metabolism, and is catalyzed by UDP-glucuronosyltransferase (UGT). So, we investigated the correlation between SXR and UGT in breast cancer cells.
We confirmed the expression of UGT1A1, UGT1A4 and UGT2B7 mRNA by RT-PCR inbreast cancer cell lines. UGT1A1 can conjugate estrogens. UGT1A4 and UGT2B7 canconjugate tamoxifen, which is the drug for hormone therapy of for breast cancer. It wasreported thatSince the expression of UGT1A1 and UGT1A4 are is regulated by SXR inhepatocellular carcinoma cell lines. W, we also studied and confirmed the up-regulation ofUGT1A4 expression by SXR in breast cancer cell lines. Furthermore, Wwe investigated theexpression levels of UGT1A1, UGT1A4 and UGT2B7 in breast cancer tissues by real-timeRT-PCR, using the specimens from 70 breast cancer patients, who were undergone theoperation in Gunma University Hospital between in 2007 and 2008. There was were nocorrelations between SXR and UGT1A1, and. There was also no correlation between SXRand UGT1A4 mRNA levels. But wWe could not measure the expression level of UGT2B7mRNA. In summary, Wwe could not obtain fund the evidence for regulation of UGT by SXRfrom this experiment plan. Because there is a fewseveral evidences of that such regulation,so we need more experiment.more study may be necessary.

Research Products

• [Journal Article] Activation of Aromatase Expression by Retinoic Acid Receptor-related Orphan Receptor (ROR)αin Breast Cancer Cells: identification of a novel ROR response elementIDENTIFICATION OF A NOVEL ROR RESPONSE ELEMENT. (2009)
  • Author(s): Hiroki Odawara, Toshiharu Iwasaki, Jun Horiguchi, Nana Rokutanda, Kazumi Hirooka, Wataru Miyazaki, Yukio Koibuchi, Noriaki Shimokawa, Yuichi Iino, Izumi Takeyoshi, Noriyuki Koibuchi
  • Journal Title: J Biologic Chem 284 Pages: 17111-9
  • Peer Reviewed
• [Journal Article] Isolated retromammary lymph node metastasis of breast cancer without axillary lymph node involvement: a case report with a false-negative sentinel lymph node biopsy. (2009)
  • Author(s): Rokutanda N, Horiguchi J, Koibuchi Y, Nagaoka R, Sato A, Odawara H, Tokiniwa H, Iino Y, Hirato J, Takeyoshi I.
  • Journal Title: Breast Cancer. 16 Pages: 162-5
  • Peer Reviewed
• [Journal Article] Augmentation of estrogen receptor-mediated transcription by steroid and xenobiotic receptor. (2008)
  • Author(s): Rokutanda N, Iwasaki T, Odawara H, Nagaoka R, Miyazaki W, Takeshita A, Koibuchi Y, Horiguchi J, Shimokawa N, Iino Y, Morishita Y, Koibuchi N.
  • Journal Title: Endocr. 33 Pages: 305-316
  • Peer Reviewed
• [Journal Article] 手術不能または再発乳癌に対するCapecitabine (Xeloda)とWeekly Paclitaxel (Taxol)の併用化学療法における容量設定試験. (2008)
  • Author(s): 堀口淳, 鯉淵幸生, 六反田奈和, 長岡りん, 菊地麻美, 佐藤亜矢子, 小田原宏樹, 石川裕子, 時庭英彰, 飯野佑一, 竹吉泉.
  • Journal Title: 癌と化療 35 Pages: 1877-1881
  • Peer Reviewed
• [Presentation] Activation of breast cancer cell proliferation by ROR-alpha through aromatase promoter. (2010)
  • Author(s): Hiroki Odawara, Jun Horiguchi, Toshiharu Iwasaki, Yukio Koibuchi, Nana Rokutanda, Wataru Miyazaki, Hideaki Tokiniwa, Yuichi Iino, Noriyuki Koibuchi, Izumi Takeyoshi.
  • Organizer: European Breast Cancer Conference 7
  • Place of Presentation: Barcelona
  • Year and Date: 20100324-20100327
• [Presentation] 乳癌組織における核内ホルモン受容体RORα発現の意義. (2009)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 佐藤亜矢子, 時庭英彰, 戸塚勝理, 飯野祐一, 鯉淵典之, 竹吉泉
  • Organizer: 第71回日本臨床外科学会総会
  • Place of Presentation: 京都
  • Year and Date: 20091119-20091121
• [Presentation] Direct interaction of RORαwith aromatase promoter in breast cancer cells. (2009)
  • Author(s): Hiroki Odawara, Jun Horiguchi, Toshiharu Iwasaki, Yukio Koibuchi, Rin Nagaoka, Nana Rokutanda, Ayako Sato, Hideaki Tokiniwa, Yuichi Iino, Noriyuki Koibuchi, Izumi Takeyoshi.
  • Organizer: Global Breast Cancer Conference 2009
  • Place of Presentation: Seoul
  • Year and Date: 20091008-20091010
• [Presentation] 乳癌組織における核内ホルモン受容体RORαとアロマターゼ発現の関係. (2009)
  • Author(s): 小田原宏樹、堀口淳、岩崎俊晴、鯉淵幸生、六反田奈和、長岡りん、佐藤亜矢子, 時庭英彰、飯野佑一、鯉淵典之、竹吉泉.
  • Organizer: 第10回ホルモンと癌研究会
  • Place of Presentation: 仙台
  • Year and Date: 20090731-20090801
• [Presentation] 核内ホルモン受容体RORαによるアロマターゼ遺伝子の新たな活性化機序. (2009)
  • Author(s): 小田原宏樹、堀口淳、岩崎俊晴、鯉淵幸生、六反田奈和、長岡りん、佐藤亜矢子、時庭英彰、戸塚勝理、飯野佑一、鯉淵典之、竹吉泉.
  • Organizer: 第19回乳癌基礎研究会
  • Place of Presentation: 群馬
  • Year and Date: 20090725-20090726
• [Presentation] 乳癌組織における核内受容体RORαの発現解析 (2009)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 佐藤亜矢子, 時庭英彰, 飯野祐一, 鯉淵典之, 竹吉泉
  • Organizer: 第17回日本乳癌学会総会
  • Place of Presentation: 東京
  • Year and Date: 20090703-20090704
• [Presentation] RORαによるアロマターゼ遺伝子の新たな活性化メカニズムの解明-乳癌への影響- (2009)
  • Author(s): 小田原宏樹、岩崎俊晴、堀口淳、鯉淵幸生、六反田奈和、長岡りん、宮崎航、飯野佑一、竹吉泉、鯉淵典之
  • Organizer: 日本内分泌学会総会
  • Place of Presentation: 群馬
  • Year and Date: 20090423-20090425
• [Presentation] 核内受容体RORαによる乳癌細胞増殖能の活性化 (2009)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 時庭英彰, 樋口徹, 飯野祐一, 鯉淵典之, 竹吉泉
  • Organizer: 日本外科学会第109回総会
  • Place of Presentation: 福岡
  • Year and Date: 20090402-20090404
• [Presentation] 術前化学療法による縮小形態が特殊であったpCRの1例 (2008)
  • Author(s): 小田原宏樹, 堀口淳, 鯉淵幸生, 長岡りん, 六反田奈和, 佐藤亜矢子, 時庭英彰, 樋口徹, 飯野佑一, 竹吉泉
  • Organizer: 日本臨床外科学会第70回総会
  • Place of Presentation: 東京
  • Year and Date: 20081127-20081129
• [Presentation] 核内受容体RORαによるアロマターゼ遺伝子の活性化とその影響 (2008)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 佐藤亜矢子, 時庭英彰, 宮崎航, 飯野佑一, 鯉淵典之, 竹吉泉
  • Organizer: 日本乳癌学会第16回総会
  • Place of Presentation: 大阪
  • Year and Date: 20080926-20080927
• [Presentation] 乳癌におけるRORαの発現とその影響-アロマターゼ遺伝子の活性化- (2008)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 佐藤亜矢子, 時庭英彰, 宮崎航, 飯野佑一, 鯉淵典之, 竹吉泉
  • Organizer: 第9回ホルモンと癌研究会
  • Place of Presentation: 岐阜
  • Year and Date: 20080620-20080621
• [Presentation] 乳癌におけるRORalphaによるアロマターゼ遺伝子発現の活性化 (2008)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 宮崎航, 時庭英彰, 飯野佑一, 鯉淵典之, 竹吉泉
  • Organizer: 日本外科学会第108回総会
  • Place of Presentation: 長崎
  • Year and Date: 20080515-20080517
• [Presentation] 乳癌における核内受容体RORαによるアロマターゼ遺伝子の活性化 (2008)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 佐藤亜矢子, 時庭英彰, 飯野祐一, 鯉淵典之, 竹吉泉
  • Organizer: 第18回群 馬clinical oncology research勉強会
  • Place of Presentation: 群馬
  • Year and Date: 2008-06-05
• [Presentation] 乳癌細胞におけるPCBによる核内ホルモン受容体を介する転写の活性化 (2007)
  • Author(s): 小田原宏樹, 堀口淳, 岩崎俊晴, 鯉淵幸生, 六反田奈和, 長岡りん, 宮崎航, 飯野佑一, 鯉淵典之, 竹吉泉
  • Organizer: 日本乳癌学会第15回総会
  • Place of Presentation: 横浜
  • Year and Date: 20070629-20070630
• [Presentation] アルドステロン産生腫瘍の術前局在診断としての副腎静脈血サンプリングの有用性 (2007)
  • Author(s): 小田原宏樹, 堀口淳, 鯉淵幸生, 長岡りん, 六反田奈和, 佐藤亜矢子, 石川裕子, 飯野佑一
  • Organizer: 日本外科学会第107回総会
  • Place of Presentation: 大阪
  • Year and Date: 20070411-20070413