Identification of novel androgen-responsive and therapeutic target genes in prostate disorders

• Project/Area Number: 21591170
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokyo
• Principal Investigator: URANO Tomohiko 東京大学, 医学部附属病院, 特任講師 (20334386)
• Co-Investigator(Kenkyū-buntansha): INOUE Satoshi 東京大学, 医学部附属病院, 特任教授 (40251251)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 癌 / シグナル伝達 / 老化 / トランスレーショナルリサーチ / プロテオーム

Research Abstract

Aging is a risk factor for prostate hyperplasia and cancer. Such disorders affect the quality of daily living and life span in the elderly. The causes of these age-related disorders are affected by genetic and environmental factors. We are focusing on the functions of sex hormone, androgen, in prostate disorders. We performed Genome-wide screening of androgen target genes in prostate cancer cells. We found that both androgen-regulated coding genes and noncoding RNAs, including Oct1, ARFGAP3, TACC2 and miR-148a. We also found that androgen-regulated ubiquitin ligase, NEDD4L and TRIM36. We infer that these genes are potential therapeutic targets in prostate cancer.

Research Products

• [Journal Article] TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer (2012)
  • Author(s): Takayama K, Horie-Inoue K, Suzuki T, Urano T, Ikeda K, Fujimura T, Takahashi S, Homma Y, Ouchi Y, Inoue S
  • Journal Title: Mol Endocrinol Volume: (in press) Issue: 5 Pages: 748-761
  • DOI: 10.1210/me.2011-1242
  • Peer Reviewed
• [Journal Article] GPR98/Gpr98 Gene Is Involved in the Regulation of Human and Mouse Bone Mineral Density (2012)
  • Author(s): Urano, T., Shiraki, M, . Yagi, H., Ito, M., Sasaki, N., Sato, M., Ouchi, Y. and Inoue, S.
  • Journal Title: J. Clin. Endocrinol. Metab Volume: 97(4) Issue: 4 Pages: E565-E574
  • DOI: 10.1210/jc.2011-2393
  • Peer Reviewed
• [Journal Article] ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration (2012)
  • Author(s): Obinata D, Takayama K, Urano T, Murata T, Ikeda K, Horie-Inoue K, Ouchi Y, Takahashi S, Inoue S
  • Journal Title: Int J Cancer Volume: 130 Issue: 10 Pages: 2240-2248
  • DOI: 10.1002/ijc.26224
  • NAID: 10031156601
  • Peer Reviewed
• [Journal Article] Clinical significance of steroid and xenobiotic receptor(SXR) and its targeted gene CYP3A4 in human prostate cancer (2012)
  • Author(s): Fujimura T, Takahashi S, Urano T, Tanaka T, Zhang W, Azuma K, Takayama K, Obinata D, Murata T, Horie-Inoue K, Kodama T, Ouchi Y, Homma Y, Inoue S
  • Journal Title: Cancer Sci Volume: 103 Issue: 2 Pages: 176-180
  • DOI: 10.1111/j.1349-7006.2011.02143.x
  • Peer Reviewed
• [Journal Article] Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer (2012)
  • Author(s): Obinata D, Takayama K, Urano T, Murata T, Kumagai J, Fujimura T, Ikeda K, Horie-Inoue K, Homma Y, Ouchi Y, Takahashi S, Inoue S
  • Journal Title: Int J Cancer Volume: 130 Issue: 5 Pages: 1021-1028
  • DOI: 10.1002/ijc.26043
  • Peer Reviewed
• [Journal Article] A single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1(HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women (2011)
  • Author(s): Urano T, Narusawa K, Sasaki N, Shiraki M, Hosoi T, Ouchi Y, Nakamura T, Inoue S
  • Journal Title: Eur Spine J Volume: 20 Issue: 4 Pages: 572-577
  • DOI: 10.1007/s00586-010-1598-0
  • Peer Reviewed
• [Journal Article] Integration of cap analysis of gene expression and chromatin immunoprecipitation analysis on array reveals genome-wide androgen receptor signaling in prostate cancer cells (2011)
  • Author(s): Takayama K, Tsutsumi S, Katayama S, Okayama T, Horie-Inoue K, Ikeda K, Urano T, Kawazu C, Hasegawa A, Ikeo K, Gojyobori T, Ouchi Y, Hayashizaki Y, Aburatani H, Inoue S
  • Journal Title: Oncogene Volume: 30 Issue: 5 Pages: 619-630
  • DOI: 10.1038/onc.2010.436
  • Peer Reviewed
• [Journal Article] Common variant s in a novel gene, FONG on chromosome 2q33. 1 confer risk of osteoporosis in Japanese (2011)
  • Author(s): Kou I, Takahashi A, Urano T, Fukui N, Ito H, Ozaki K, Tanaka T, Hosoi T, Shiraki M, Inoue S, Nakamura Y, Kamatani N, Kubo M, Mori S, Ikegawa S
  • Journal Title: PLoS ONE Volume: 6 Issue: 5 Pages: e19641-e19641
  • DOI: 10.1371/journal.pone.0019641
  • Peer Reviewed
• [Journal Article] PROX1 suppresses vitamin K-induced transcriptional activity of steroid and xenobiotic receptor (2011)
  • Author(s): Azuma K, Urano T, Watabe T, Ouchi Y, Inoue S
  • Journal Title: Genes Cells Volume: 16 Issue: 11 Pages: 1063-1070
  • DOI: 10.1111/j.1365-2443.2011.01551.x
  • Peer Reviewed
• [Journal Article] A single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women (2011)
  • Author(s): Urano T, Narusawa K, Sasaki N, Shiraki M, Hosoi T, Ouchi Y, Nakamura T, Inoue S
  • Journal Title: Eur Spine J Volume: 20 Pages: 572-577
  • Peer Reviewed
• [Journal Article] Common variant s in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese (2011)
  • Author(s): Kou I, Takahashi A, Urano T, Inoue S, Ikegawa S, et al.
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Integration of cap analysis of gene expression and chromatin immunoprecipitation analysis on array reveals genome-wide androgen receptor signaling in prostate cancer cells. (2011)
  • Author(s): Takayama K, Urano T, Inoue S, et al.
  • Journal Title: Oncogene Volume: 30 Pages: 619-630
  • Peer Reviewed
• [Journal Article] A single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN 1) gene is associated with spinal osteophyte formation and disc deeeneration in Jananese women. (2011)
  • Author(s): Urano T, Nakamura K, Inoue S, et al.
  • Journal Title: Eur Spine J Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Octl regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer. (2011)
  • Author(s): Obinata D, Urano T, Inoue S, et al.
  • Journal Title: Int J Cancer Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Identification of non-synonymous polymorphisms in the WDSOF1 gene as novel susceptibility markers for low bone mineral density in Japanese postmenopausal women (2010)
  • Author(s): Urano T, Shiraki M, Usui T, Sasaki N, Ouchi Y, Inoue S
  • Journal Title: Bone Volume: 47 Issue: 3 Pages: 636-642
  • DOI: 10.1016/j.bone.2010.06.017
  • Peer Reviewed
• [Journal Article] miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression (2010)
  • Author(s): Murata T, Takayama K, Katayama S, Urano T, Horie-Inoue K, Ikeda K, Takahashi S, Kawazu C, Hasegawa A, Ouchi Y, Homma Y, Hayashizaki Y, Inoue S
  • Journal Title: Prostate Cancer Prostatic Dis Volume: 13 Issue: 4 Pages: 356-361
  • DOI: 10.1038/pcan.2010.32
  • Peer Reviewed
• [Journal Article] Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption (2010)
  • Author(s): Azuma K, Casey SC, Ito M, Urano T, Horie K, Ouchi Y, Kirchner S, Blumberg B, Inoue S
  • Journal Title: J Endocrinol Volume: 207 Issue: 3 Pages: 257-263
  • DOI: 10.1677/joe-10-0208
  • Peer Reviewed
• [Journal Article] Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells (2010)
  • Author(s): Azuma K, Urano T, Ouchi Y, Inoue S
  • Journal Title: Endocrine Journal Volume: 57 Issue: 5 Pages: 455-462
  • DOI: 10.1507/endocrj.K09E-290
  • NAID: 130004443628
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Identification of non-synonymous polymorphisms in the WDSOF1 gene asnovel susceptibility markers for low bone mineral density in Japanese postmenopausal women. (2010)
  • Author(s): Urano T, Shiraki M, Inoue S, et al.
  • Journal Title: Bone Volume: 47 Pages: 636-642
  • Peer Reviewed
• [Journal Article] miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CANDI expression. (2010)
  • Author(s): Murata T, Urano T, Inoue S, et al.
  • Journal Title: Prostate Cancer Prostatic Dis Volume: 13 Pages: 356-361
  • Peer Reviewed
• [Journal Article] Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorotion. (2010)
  • Author(s): Azuma K, Urano T, Inoue S, et al.
  • Journal Title: J Endocrinol Volume: 207 Pages: 257-263
  • Peer Reviewed
• [Journal Article] Glucocorticoid-induced gene tripartite motif-containing 63(TRIM63)promotes differentiation of osteoblastic cells. (2010)
  • Author(s): Azuma K, Urano T, Inoue S, et al
  • Journal Title: Endocr J (In press)
  • NAID: 10029584941
  • Peer Reviewed
• [Journal Article] Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I (2009)
  • Author(s): Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, Garcia-Sastre A
  • Journal Title: Cell Host Microbe Volume: 5 Issue: 5 Pages: 439-449
  • DOI: 10.1016/j.chom.2009.04.006
  • Peer Reviewed
• [Journal Article] TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase (2009)
  • Author(s): Urano T, Usui T, Takeda S, Ikeda K, Okada A, Ishida Y, Iwayanagi T, Otomo J, Ouchi Y, Inoue S
  • Journal Title: Biochem Biophys Res Commun Volume: 383 Issue: 2 Pages: 263-268
  • DOI: 10.1016/j.bbrc.2009.04.010
  • Peer Reviewed
• [Journal Article] TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase. (2009)
  • Author(s): Urano T, Usui T, Inoue S, et al
  • Journal Title: Biochem Biophys Res Commun 383 Pages: 263-268
  • Peer Reviewed
• [Journal Article] Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I. (2009)
  • Author(s): Gack MU, Urano T, Inoue S, Garcia-Sastre A, et al
  • Journal Title: Cell Host Microbe 5 Pages: 439-449
  • Peer Reviewed
• [Journal Article] GPR98/Gpr98 gene is involved in the regulation of human and mouse bone mineral density
  • Author(s): Urano T, Shiraki M, Ouchi Y, Inoue S, et al.
  • Journal Title: J Clin Endocrinol Metab Volume: (in press)
  • Peer Reviewed
• [Journal Article] TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer
  • Author(s): Takayama K, Horie-Inoue K, Urano T, Inoue S, et al.
  • Journal Title: Mol Endocrinol Volume: (in press)
  • Peer Reviewed
• [Presentation] [Symposium] Genome-wide Androgen Signaling in Prostate Cancer (2011)
  • Author(s): Inoue S
  • Organizer: The 42^<nd> International Symposium of The Princess Takamatsu Cancer Research Fund
  • Place of Presentation: Tokyo, Japan
• [Presentation] Genome-wide androgen receptor signaling in prostate cancer (2011)
  • Author(s): Inoue S
  • Organizer: US-Japan conference on inflammation, diabetes and cancer
  • Place of Presentation: Duarte, California, USA
• [Presentation] スクレロスチンの血中濃度は骨量、脊椎変形ならびに体脂肪量と正に相関し、SOST遺伝子近傍のSNPとも関連する (2011)
  • Author(s): 浦野友彦、白木正孝、成澤研一郎、中村利孝、大内尉義、井上聡
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
• [Presentation] [シンポジウム]骨粗鬆症のCNV解析 (2011)
  • Author(s): 浦野友彦、白木正孝、大内尉義、井上聡
  • Organizer: 遺伝医学合同学術集会
  • Place of Presentation: 京都
• [Presentation] [優秀演題賞受賞]葉酸代謝関連マーカーを用いた骨折リスクの解析 (2011)
  • Author(s): 浦野友彦、白木正孝、斎藤充、大内尉義、井上聡
  • Organizer: 第53回日本老年医学会学術集会
  • Place of Presentation: 東京
• [Presentation] GPR98 gene in the regulation of human and mouse bone mineral density (2011)
  • Author(s): Urano T, Shiraki M, Yagi H, Ito M, Sato M, Ouchi Y, Inoue S
  • Organizer: ENDO 2011 : The 93rd Annual Meeting & Expo
  • Place of Presentation: Boston, USA
• [Presentation] [研究助成受賞講演]骨・関節における加齢状態を予測するゲノムマーカーならびにバイオマーカーの探索と同定 (2011)
  • Author(s): 浦野友彦、白木正孝、大内尉義、井上聡
  • Organizer: 第11回日本抗加齢医学会総会
  • Place of Presentation: 京都
• [Presentation] エストロゲン受容体αならびにLRP5遺伝子における遺伝子多型を用いた高齢女性における脊柱変形のリスク評価 (2011)
  • Author(s): 浦野友彦、白木正孝、成澤研一郎、大内尉義、中村利孝、井上聡
  • Organizer: 第11回日本抗加齢医学会総会
  • Place of Presentation: 京都
• [Presentation] [Symposium] Genome-wide androgen signaling (2011)
  • Author(s): Inoue S
  • Organizer: 5th PacRim Breast and Prostate Cancer Meeting
  • Place of Presentation: Kingscliff, NSW, Australia
• [Presentation] 骨・関節における加齢状態を予測するゲノムマーカーならびにバイオマーカーの探索と同定 (2011)
  • Author(s): 浦野友彦、白木正孝、大内尉義、井上聡
  • Organizer: 第11回日本抗加齢医学会総会
  • Place of Presentation: 京都(研究助成受賞講演)
• [Presentation] 葉酸代謝関連マーカーを用いた骨折リスクの解析 (2011)
  • Author(s): 浦野友彦、白木正孝、斎藤充、大内尉義、井上聡
  • Organizer: 第53回日本老年医学会学術集会
  • Place of Presentation: 東京(優秀演題賞受賞)
• [Presentation] 骨粗鬆症のCNV解析 (2011)
  • Author(s): 浦野友彦、白木正孝、大内尉義、井上聡
  • Organizer: 遺伝医学合同学術集会2011
  • Place of Presentation: 京都(シンポジウム)(招待講演)
• [Presentation] スクレロステンの血中濃度は骨量、脊椎変形ならびに体脂肪量と正に相関し、SOST遺伝子近傍のSNPとも関連する (2011)
  • Author(s): 浦野友彦、白木正孝、成澤研一郎、中村利孝、大内尉義、井上聡
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Genome-wide androgen signaling (2011)
  • Author(s): Inoue S
  • Organizer: 5th PacRim Breast and Prostate Cancer Meeting
  • Place of Presentation: Kingscliff, NSW, Australia(Symposium)(招待講演)
• [Presentation] Genome-wide Androgen Signaling in Prostate Cancer (2011)
  • Author(s): Inoue S
  • Organizer: The 42^<nd> International Symposium of The Princess Takamatsu Cancer Research Fund
  • Place of Presentation: Tokyo, Japan(Symposium)(招待講演)
• [Presentation] SNPアレイを用いた骨量との関連解析-ヒトゲノム、マウスモデル、ならびに発現解析を用いた骨粗鬆症疾患関連遺伝子の同定 (2010)
  • Author(s): 浦野友彦、白木正孝、八木秀司、佐藤真、大内尉義、井上聡
  • Organizer: 第12回日本骨粗鬆症学会
  • Place of Presentation: 大阪
• [Presentation] Large scale human SNP analysis revealed an association of GPR98 gene polymorphisms with bone mineral density in postmenopausal women and Gpr98 deficient mice display osteopenia (2010)
  • Author(s): Urano T, Shiraki M, Yagi H, Sato M, Ouchi Y, Inoue S
  • Organizer: American Society of Bone and Mineral Research 32^<nd> Annual Meeting
  • Place of Presentation: Toronto, Ontario, Canada
• [Presentation] 葉酸トランスポーター遺伝子多型は血中葉酸値を規定し骨粗鬆症ならびに骨折発症に関わる (2010)
  • Author(s): 浦野友彦、白木正孝、大内尉義、井上聡
  • Organizer: 第10回日本抗加齢医学会総会
  • Place of Presentation: 京都
• [Presentation] 葉酸トランスポーター遺伝子多型は血中葉酸値を規定し骨粗鬆症ならびに骨折発症に関わる (2010)
  • Author(s): 浦野友彦、白木正孝、大内尉義、井上聡
  • Organizer: 第10回日本抗加齢医学会総会
  • Place of Presentation: 京都国際会館(京都)
• [Presentation] Large scale human SNP analysis revealed an association of GPR98 gene polymorphisms with bone mineral density in postmenopausal women and Gnr98 deficient mice display osteonenia. (2010)
  • Author(s): Urano T, Shiraki M, Yagi H, Sato M, Ouchi Y, Inoue S
  • Organizer: American Society of Bone and Mineral Research 32^<nd> Annual Meeting
  • Place of Presentation: Toronto, Ontario, Canada
• [Presentation] SNPアレイを用いた骨量との関連解析-ヒトゲノム、マウスモデル、ならびに発現解析を用いた骨粗霧症疾患関連遺伝子の同定 (2010)
  • Author(s): 浦野友彦、白木正孝、八木秀司、佐藤真、大内尉義、井上聡
  • Organizer: 第12回日本骨粗鬆症学会
  • Place of Presentation: 大阪国際会議場(大阪)
• [Presentation] Estrogen-responsive finger protein as a tumor-promoting factor and a therapeutic target for breast cancer. (2009)
  • Author(s): Urano T, Tsukui T, Inoue S, et al
  • Organizer: 第68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: 2009-10-01
• [Presentation] Estrogen-responsive finger protein as a tumor-promoting factor and a therapeutic target for breast cancer (2009)
  • Author(s): Urano T, Tsukui T, Usui T, Ikeda K, Takayama K, Azuma K, Ouchi Y, Inoue S
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜