2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38010JC virus is a member of the human polyomaviruses. The lifecycle of JC virus contains 2 types: permissive cycle and non-permissive cycle. (1) If JC virus infects permissive cells, JCV large tumor antigen (LT) expression orchestrates events leading to viral replication, virion formation, and subsequent lysis and destruction of the host cells. For example, JC virus infects human brain oligodendrocytes succumbing to progressive multifocal leukoencephalopathy. (2) If JCV T-antigen is expressed in a cell in the absence of viral replication, large tumor antigen (Tag) may interact with host regulatory proteins to result in cellular transformation and ultimately uncontrolled proliferation. JCV could exhibit oncogenic potential demonstrated in some animal studies. Earlier reports found that JCV LT binding to p53 or pRB proteins affected host cell cycle control by using coimmunoprecipitation in cell lines. Recently, JCV DNA was detected in some human cancers such as transitional cell carcinomas of the bladder, adenocarcinomas of the prostate and colorectal adenocarcinomas. Those studies indicated that JCV might involve the carcinogenesis of human malignancy. Our current study found JCV DNA was present in human lung cancer cells, meanwhile JCV LT was expressed and VP1 (virion capsid protein) was not. Thus, the purpose of this project is to understand the role of JCV in human lung carcinogenesis. To achieve the purpose, we propose a three-year project. The specific aims are: 1. To investigate the relationship between JCV-related oncogenic factors and human lung cancers. 2. To investigate the JCV LT expression correlated to cellular transformation in human bronchial cell lines. 3. To identify specific oncogenes or tumor suppressor genes associated with JCV LT expression during human lung carcinogenesis.JC 病毒是人類多瘤性病毒的一員。已知JC 病毒生命週期包括二種形式：(1)當病毒感 染允許性 (permissive)細胞後，病毒子代將會在細胞核產生，並且溶解該細胞已釋放出 病毒顆粒。JC 病毒感染人類腦寡突細胞 (oligodendrocytes) ，並且溶解該細胞導致進行 性多病兆腦白質症 (progressive multifocal leukoencephalopathy)。 (2) 當病毒感染非允許 性 (non-permissive)細胞後，病毒子代並不會產生且該細胞也不會溶解，反而經由早期 蛋白， 大腫瘤抗原(large tumor antigen, LT) ， 進行該細胞惡性轉型 (malignant transformation)。 JCV 具有癌化的特性，已在動物實驗中獲得證實。JCV LT 參與癌化的 細胞內機轉，亦有相關文獻佐證。近年來JCV DNA 也在多種人類惡性腫瘤細胞中偵測 出來，且同時有LT 的表達，例如：腦腫瘤，大腸癌，前列腺癌。這些研究結果顯示， JCV 可能參與人類細胞癌化的過程。本實驗近年來發現人類肺癌細胞中，有JCV DNA 的存在，且同時有LT 的表達。因此，本計畫的目的是瞭解JCV 於肺癌癌化過程中，所 扮演的角色。我們提出三年計畫，預計完成下列工作： 1. 瞭解已知JCV 癌化相關的調控蛋白與肺癌的關聯性。 2. 瞭解JCV 表現程度與肺細胞轉型 (transformation)之關係。 3. 找出肺癌癌化過程中，因JCV LT 表達而受影響的致癌基因或抑癌基因，然後在臨床 肺癌組織中檢測這些基因的表現。Project