Involvement of androgen receptor and unfolded protein response in human liver and pancreatic cancers

• Project/Area Number: 24590955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: KANDA TATSUO 千葉大学, 医学(系)研究科(研究院), 講師 (20345002)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アンドロジェンレセプター / 小胞体ストレス / 自然免疫 / 肝細胞癌 / 膵癌 / C型肝炎ウイルス / GRP78 / アポトーシス / 肝癌 / Ｓｏｒａｆｅｎｉｂ / AR

Outline of Final Research Achievements

(1) Endoplasmic reticulum (ER) stress response plays a key role in hepatic cell damage induced by an innate immune response. (2) Androgen receptor (AR) and ER-stress response are cooperatively involved in human liver cancer, one of the male-dominant cancers. (3) Hepatitis C virus (HCV) infection enhances GRP78 expression, which confers to the resistance against apoptosis in HCV-infected hepatocytes. (4) ER stress response plays an important role in pancreatic cancer cell line KP-2, in which AR highly expresses.

Research Products

• [Journal Article] The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells. (2015)
  • Author(s): Jiang X, Kanda T, Nakamoto S, Saito K, Nakamura M, Wu S, Haga Y, Sasaki R, Sakamoto N, Shirasawa H, Okamoto H, Yokosuka O
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中 Issue: 4 Pages: 908-912
  • DOI: 10.1016/j.bbrc.2015.02.058
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis C Virus Nonstructural Protein 5A Inhibits Thapsigargin-Induced Apoptosis (2014)
  • Author(s): Xia Jiang, Tatsuo Kanda, Shuang Wu, Shingo Nakamoto, Takaji Wakita, Hiroshi Shirasawa, Osamu Yokosuka.
  • Journal Title: PLoS ONE Volume: 9 Issue: 11 Pages: e113499-e113499
  • DOI: 10.1371/journal.pone.0113499
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Knockdown of glucose-regulated protein 78 enhances poly(ADP-ribose) polymerase cleavage in human pancreatic cancer cells exposed to endoplasmic reticulum stress. (2014)
  • Author(s): XIA JIANG, TATSUO KANDA, SHINGO NAKAMOTO, YUKI HAGA, REINA SASAKI, MASATO NAKAMURA, SHUANG WU, RINTARO MIKATA, OSAMU YOKOSUKA.
  • Journal Title: Oncology Reports Volume: 32 Issue: 6 Pages: 2343-2348
  • DOI: 10.3892/or.2014.3533
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Androgen receptor signaling in hepatocellular carcinoma and pancreatic cancers. (2014)
  • Author(s): Tatsuo Kanda, Xia Jiang, Osamu Yokosuka
  • Journal Title: World Journal of Gastroenterology Volume: 20 Pages: 9229-9236
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppression of La Antigen Exerts Potential Antiviral Effects against Hepatitis A Virus. (2014)
  • Author(s): Jiang X, Kanda T, Wu S, Nakamoto S, Saito K, Shirasawa H, Kiyohara T, Ishii K, Wakita T, Okamoto H, Yokosuka O.
  • Journal Title: PLoS One. Volume: 9 Issue: 7 Pages: e101993-e101993
  • DOI: 10.1371/journal.pone.0101993
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of androgen receptor and glucose-regulated protein 78kDa in human hepatocarcinogenesis (2014)
  • Author(s): Xia Jiang, Tatsuo Kanda, Shingo Nakamoto, Tatsuo Miyamura, Shuang Wu, Osamu Yokosuka.
  • Journal Title: Experimental Cell Research Volume: 323 Issue: 2 Pages: 326-336
  • DOI: 10.1016/j.yexcr.2014.02.017
  • Peer Reviewed
• [Journal Article] Ultra-deep sequencing analysis of the hepatitis A virus 5'-untranslated region among cases of the same outbreak from a single source (2013)
  • Author(s): Wu S., et al.
  • Journal Title: Int J Med Sci. Volume: 11 Issue: 1 Pages: 60-64
  • DOI: 10.7150/ijms.7728
  • Peer Reviewed / Open Access
• [Journal Article] Lipopolysaccharide blocks induction of unfolded protein response in hum an hepatoma cell lines (2013)
  • Author(s): Jiang X., et al.
  • Journal Title: Immunol Lett. Volume: 152 Issue: 1 Pages: 8-19
  • DOI: 10.1016/j.imlet.2013.03.006
  • Peer Reviewed
• [Journal Article] Androgen Receptor and Hepatocellular Carcinoma (2013)
  • Author(s): Tatsuo Kanda, Osamu Yokosuka, Masao Omata
  • Journal Title: Gastrointestinal & Digestive System Volume: S12 Issue: S12
  • DOI: 10.4172/2161-069x.s12-012
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide blocks induction of unfolded protein response in human hepatoma cell lines (2013)
  • Author(s): Xia Jiang, Tatsuo Kanda, Takeshi Tanaka, Shuang Wu, Shingo Nakamoto, Fumio Imazeki, Osamu Yokosuka
  • Journal Title: Immunology Letters Volume: in press
  • Peer Reviewed
• [Presentation] 肝癌におけるAndrogen receptor (AR)を介したERストレスに関する検討 (2013)
  • Author(s): 姜霞, 神田達郎, 横須賀收
  • Organizer: 日本消化器病学会関連研究会第9回消化器病における性差医学・医療研究会
  • Place of Presentation: 大阪大学中之島センター10階佐治敬三メモリアルホール