Searching for the novel therapeutic targets in pituitary tumors

• Project/Area Number: 16K09810
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kitasato University
• Principal Investigator: TANI YUJI 北里大学, 医学部, 助教 (30456214)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 下垂体腫瘍 / 内分泌学

Outline of Final Research Achievements

We focused on PLZF as a targeting factor in pituitary tumors. PLZF was expressed in mouse pituitary and GH producing pituitary tumor cell lines (GH3). Using GH3 cells, we searched for the localization and the factors that regulate nuclear-cytoplasmic shuttling of PLZF. We examined the downstream signals of PLZF and revealed interaction between PLZF and LDL receptor. We identified a PLZF binding site upstream of the LDL receptor and proceeded with detailed analysis using ChIP-seq.

Academic Significance and Societal Importance of the Research Achievements

下垂体腫瘍の代表疾患である先端巨大症やクッシング病への治療選択肢は広がりつつあるが、治療困難例や薬剤抵抗性を示す症例もあり、新たな治療標的分子の探索は不可欠である。ホルモンの正常化に加え、腫瘍増殖の抑制効果を併せ持つ標的因子が望まれている。