Diagnostic and therapeutic application of p53 family in esophageal squamous cell carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09354
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Sasaki Yasushi 札幌医科大学, 医療人育成センター, 教授 (70322328)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: p53 / p53ファミリー / 食道扁平上皮癌 / NGS

Outline of Final Research Achievements

Genome sequencing studies of cancer have revealed the genomic landscapes of human cancer and have shown that the p53 tumor suppressor gene is most frequently mutated in cancers among the human genes. The p53 family is composed of a group of transcription factors, p53, p73, and p63. A high frequency of p53 mutation has been reported in esophageal squamous cell carcinoma (ESCC). Therefore, loss of p53 function is thought to be very important in ESCC. To identify the direct transcriptional targets of p53 family, we performed RNA sequencing (RNA-seq), chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) analyses and other functional assays. We have isolated several p53 family target transcripts, including protein-coding genes and non-coding RNAs. Our results indicated a p53 family-mediated transcriptional network involved in various biological functions and tumor suppression.

Free Research Field

がん関連遺伝子

Academic Significance and Societal Importance of the Research Achievements

p53はヒト腫瘍において最も高頻度に変異を認めるがん抑制遺伝子である．予後不良な消化器癌である食道扁平上皮癌では70％以上の症例でp53変異が認められるが，変異p53自体は治療標的とはならず，有効な分子標的薬も存在しない．本研究では，食道扁平上皮癌においてp53ネットワーク破綻にともなって変化するトランスクリプトーム（蛋白コード遺伝子，非コードRNA）を網羅的に分析し，個々の関連分子の機能解析を行った．本研究結果は，p53 ネットワークによる腫瘍抑制メカニズムのさらなる理解とそれを標的とした食道扁平上皮癌の治療法開発の基盤形成につながる．