Role of PYCARD, an apoptosis-inducing gene, in prostatic tumorigenesis

• Project/Area Number: 18K07061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tohoku University
• Principal Investigator: Fukushige Shinichi 東北大学, 医学系研究科, 特任教授 (90192723)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌 / ゲノム / 遺伝子 / 前立腺癌 / PYCARD / DNAメチル化 / モデルマウス / アポトーシス / 発現制御

Outline of Final Research Achievements

Using mouse model of prostate cancer, we aimed to clarify the role of PYCARD gene, which shows promoter hypermethylation and inactivation in human prostate cancer. Although further analysis is needed to draw conclusions due to the small number of individuals, the genotype of Pycard may influence precancerous lesions and tumor size in prostate cancer in prostate-specific Pten knockout mice.
On the other hand, analysis of human prostate cancer tissue suggested that inactivation of PYCARD may already occur in precancerous lesions and that aberrant DNA methylation of PYCARD is a distinctive feature of prostate cancers with Gleason score >= 7.

Academic Significance and Societal Importance of the Research Achievements

本研究によりジェネティックな異常だけでなくエピジェネティックな異常が前立腺癌の発生・進展に重要な役割を果たし、PYCARDプロモーター領域の高メチル化、PYCARD不活化によるアポトーシス阻害が前立腺癌の前癌病変、腫瘍形成を促進する可能性が示された。PYCARDは、前立腺癌の診断、治療のターゲットになる可能性もあることからさらなる検討が必要である。

Research Products

• [Int'l Joint Research] University of Rochester(米国)
• [Int'l Joint Research] Emory University School of Medicine(米国)
• [Int'l Joint Research] Emory University(米国)
• [Journal Article] Aberrant hypermethylation-mediated suppression of PYCARD is extremely frequent in prostate cancer with Gleason score >=7 (2021)
  • Author(s): Toshiya Miyauchi, Masahiro Takahashi, Koji Mitsuzuka, Yuriko Saiki, Teppei Okubo, Paula M. Vertino, Akiteru Goto, Yoichi Arai, Akira Horii, and Shinichi Fukushige
  • Journal Title: Disease Markers Volume: 2021 Pages: 1-13
  • DOI: 10.1155/2021/8858905
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] アポトーシス誘導遺伝子PYCARDは前立腺癌でDNA高度メチル化により発現抑制される (2019)
  • Author(s): 宮内隼弥、高橋正博、大久保鉄平、齋木由利子、三塚浩二、荒井陽一、堀井明、福重真一
  • Organizer: 第108回日本病理学会総会
• [Presentation] IRX1の異常メチル化は前立腺癌に高頻度で発生し、増殖を活性化する (2019)
  • Author(s): 高橋正博、三塚浩二、伊藤明宏、堀井明、福重真一
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] PYCARDは前立腺癌において異常にメチル化し、発現低下している (2019)
  • Author(s): 福重真一、宮内隼弥、高橋正博、齋木由利子、大久保鉄平、三塚浩二、荒井陽一、堀井明
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] ZNF750 gene promoter is aberrantly methylated in prostate cancer (2018)
  • Author(s): 高橋正博、三塚浩二、齋木由利子、堀井明、荒井陽一、福重真一
  • Organizer: 第77回日本癌学会学術総会
• [Remarks] Department of Molecular Pathology
  • URL: http://www.molpath.med.tohoku.ac.jp