Basic studies on TOPK as a target molecule of cancer

• Project/Area Number: 20590401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Ehime University
• Principal Investigator: ABE Yasuhito Ehime University, 大学院・医学系研究科, 准教授 (30184229)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: TOPK / 乳癌 / 増殖 / 悪性度 / 腫瘍 / シグナル

Research Abstract

Purpose: A MAPKK-like mitotic protein kinase, TOPK, plays a pivotal role in the growth and movement of cancer cells. As is evidenced by clinical application of anti-HER2-monoclonal antibody, EGF-R/HER2 mediates an important signaling in the proliferation and invasion of breast cancer cells through MAPK- and PI3K- signaling. Raf, an imperative member of MAPK signaling, binds to TOPK, although, significance of this interaction has not been elucidated. In this study, we analyzed expression of TOPK and investigated biological significance of TOPK-Raf interaction using breast cancer cells.
Experimental Design: We analyzed the expression of TOPK in the clinical breast cancer tissues and investigated MAPK-signaling from the aspect of TOPK and Raf in breast cancer cells.
Results: Immunohistochemical analysis revealed that the peak-expression intensity of TOPK correlated with the Histologic Grade of human invasive ductal carcinoma of breast. Our results suggested that Raf phosphorylates TOPK at Thr-198, a critical residue for kinase activity of TOPK and that TOPK enhances MAPK signaling by upregulating Ras binding to Raf.
Conclusions: TOPK is indicated to play an important role in the malignant potential of breast cancer via EGF-R/HER2 signaling. This study suggests that TOPK can be a molecular target for breast cancer therapy in the future.

Research Products

• [Journal Article] Serum anti-PDIK1L autoantibody as a novel marker for endometriosis (2010)
  • Author(s): Nabeta, M., Abe, Y., Haraguchi, R., Kito, K., Kusanagi, Y., Ito, M.
  • Journal Title: Fertility and Sterility 94 Pages: 2552-2557
  • Peer Reviewed
• [Journal Article] Serum anti PDIK1L autoantibody as a novel marker for endometriosis. (2010)
  • Author(s): M.Nabeta, Y.Abe, et al.
  • Journal Title: Fertil Steril. Volume: 94 Pages: 2552-2557
  • Peer Reviewed
• [Journal Article] ADP-ribosylation factor like 7(ARL7)interacts with α-tubulin and modulates intracelluar vesicular transport (2009)
  • Author(s): Wei, et al.
  • Journal Title: Biochemical and Biophysical Research Communications 384 Pages: 352-356
  • Peer Reviewed
• [Journal Article] Neither MafA/L-Maf nor MafB is essential for lens development in mice (2009)
  • Author(s): Takeuchi et, al.
  • Journal Title: Gene to Cells 14 Pages: 941-947
  • Peer Reviewed