Mechanism of endoplasmic reticulum stress and tumor progression in renal cell carcinoma

2013 Fiscal Year Final Research Report

• Project/Area Number: 22791506
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: National Defense Medical College
• Principal Investigator: KURODA Kenji 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 病院, 助教 (10306780)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: 小胞体ストレス / 低酸素ストレス / GRP78 / IRE1 / 腎細胞癌

Research Abstract

In renal cell carcinoma (RCC), it was reported that HIF-VEGF signaling pathway could be under the control of endoplasmic reticulum stress (ER stress). Strong expression of GRP78 was also reported to play an important role in ER stress for RCC. In 2010, we investigated the relationship between expression level of GRP78 and clinicopathological parameters using RCC specimens. Statistically significant association was found between GRP78 positivity and higher tumor grade, advanced T stage, lymphovascular invasion, regional nodal involvement, and distant metastasis. Positivity of GRP78 expression was significantly associated with shorter disease-specific and progression-free survival.
Representative RCC cell lines such as Caki-1, 786O, A498, 769P showed strong expression of GRP78 and IRE1 among ER stress-related proteins. It seemed that the expression of HIF1 and HIF2 were influenced by that of IRE1. So far, inhibition of GRP78 and IRE1 could lead to more anticancer effect on RCC cells.

Research Products

• [Journal Article] Glucose-Regulated Protein 78 Positivity as a Predictor of Poor Survival in Patients with Renal Cell Carcinoma (2011)
  • Author(s): Kenji Kuroda, Akio Horiguchi, Takako Asano, Keiichi Ito, Junichi Asakuma, Akinori Sato, Hidehiko Yoshii, Masamichi Hayakawa, Makoto Sumitomo, Tomohiko Asano
  • Journal Title: Urologia Internationalis Volume: 87(4) Pages: 450-456
• [Presentation] IMPACT OF INCREASED EXPRESSION OF GLUCOSE-REGULATED PROTEIN 78 ON CLINICOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN RENAL CELL CARCINOMA (2011)
  • Author(s): Kenji Kuroda, Akio Horiguchi, Takako Asano, Shinsuke Tasaki, Junichi Asakuma, Hidehiko Yoshii, Akinori Sato, Keiichi Ito, Kenji Seguchi, Makoto Sumitomo, Tomohiko Asano
  • Organizer: 2011 Annual Meeting of the American Urological Association
  • Place of Presentation: Washington DC
  • Year and Date: 20110514-19
• [Presentation] 腎細胞癌におけるGRP78発現の検討 (2011)
  • Author(s): 黒田健司, 堀口明男, 田崎新資, 吉井秀彦, 佐藤全伯, 朝隈純一, 伊藤敬一, 瀬口健至, 早川正道, 住友誠, 浅野友彦
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20110421-24
• [Presentation] 防衛医科大学校における進行性腎細胞癌に対する分子標的治療薬の治療成績 (2011)
  • Author(s): 吉井秀彦, 伊藤敬一, 黒田健司, 佐藤全伯, 朝隈純一, 堀口明男, 瀬口健至, 辻明,住友誠, 早川正道, 浅野友彦
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 第99 回日本泌尿器科学会総会
  • Year and Date: 20110421-24