Treatment research by the suppression of secretory phenomenon associated with cellular senescence in mouse prostate cancer model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Juntendo University (2023); Dokkyo Medical University (2021-2022)
• Principal Investigator: Ide Hisamitsu 順天堂大学, 医学部, 特任教授 (00301383)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 前立腺癌

Outline of Final Research Achievements

Using a novel prostate cancer onset model in which the DNA demethylation enzyme UTX was specifically knocked out in the prostate, we investigated whether SASP (senescence-associated secretory phenotype) induced by fat loading and aging contributes to the malignancy and acquisition of castration resistance in prostate cancer cells. As a model, we created prostate-specific Utx-deficient mice. In male mice with prostate-specific Utx deletion, prostate cancer development was observed due to the stress from a high-fat diet. Prostate cancer occurred after 8-9 weeks, with a malignancy graded at Gleason grade 3-4. Using senescence-associated β-galactosidase (SA β-Gal) as an aging marker and evaluating through immunohistochemical staining, an increase in β-Gal positive cells was observed with cancer development. These research results suggest a mechanism of cancer progression mediated by SASP in Utx-deficient mice.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

モデルとして、前立腺特異的なUtx欠失マウスを作製し、前立腺でUtxを欠失したオスマウスでは、脂肪食によるストレスから前立腺癌の発癌がみられた。ヒストン・クロマチン修飾因子を標的とした前立腺癌モデルマウスはまったく新しい疾患モデルになると考えられ、SASPの解析とともに得られた結果は前立腺癌発症の分子機構に新たな知見をもたらし、新規治療法開発に役立つ可能性が期待される。