Functional Analysis of Apoptosis Regulatory Factor GRIM19 in Oral Carcinoma Cells

• Project/Area Number: 25462929
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Meikai University
• Principal Investigator: Mori Kazumasa 明海大学, 歯学部, 講師 (80372902)
• Co-Investigator(Kenkyū-buntansha): Yoshihiro Ohmori 明海大学, 歯学部, 教授 (50194311)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: GRIM19 / 扁平上皮癌 / アポトーシス / ＩＦＮ / オートファジー / STAT3 / GRIM-19 / IFN / Lactacystin / rapamycin

Outline of Final Research Achievements

We have investigated the expression of the GRIM-19 in oral squamous cell carcinoma cell lines and found a low-GRIM-19 expression cell line (HSC-2) and a high- GRIM-19 expression cell line (Ca9-22). Our results also suggested that the expression of the GRIM-19 is regulated at the protein levels but not transcriptional level. To determine the regulatory mechanism for the expression of GRIM-19 protein, we analyzed the involvement of ubiquitin-proteasome systems and autophagy system using various inhibitors. The results demonstrated that the expression of GRIM-19 protein unregulated by treatment with the proteasome and the autophagy inhibitors in Ca9-22 cells. However neither the proteasome inhibitor nor the autophagy inhibitor enhanced the expression in HSC-2 cells. These results suggest a possibility that the impaired expression of GRIM-19 in HSC-2 cells is due to a mutation in the cording region of the GRIM-19 gene.

Research Products

• [Journal Article] Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment. (2015)
  • Author(s): Kazumasa Mori, Shigeki Haragchi, Miki Hiroi, Yoshihiro Ohmori
  • Journal Title: BMC Cancer Volume: 15
  • DOI: 10.1186/s12885-015-1587-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 口腔癌細胞におけるアポトーシス制御因子GRIM19の発現制御機構 (2014)
  • Author(s): 森 一将
  • Organizer: 第59回 公益社団法人 日本口腔外科学会総会・学術大会
  • Place of Presentation: 千葉県 千葉市 幕張メッセ国際会議場
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] 口腔癌細胞におけるアポトーシス制御因子GRIM19の発現制御機構 (2014)
  • Author(s): 森 一将
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡県 福岡市 福岡国際会議場
  • Year and Date: 2014-09-24 – 2014-09-27