Analysis of Co-factors for Cervical Viral Oncogenesis

宫颈病毒癌发生的辅助因素分析

• 批准号: 05671380
• 负责人: IWASAKA Tsuyoshi
• 金额: $ 1.41万
• 依托单位: Saga Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671380/
• 关键词: cervical carcinoma; human papillomavirus; co-factor; oncogene; anti-oncogene; immortalization; oncogenesis; 子宮頸癌; ヒトパピローマ ウイルズ; 不死化細胞

(1) Four immortalized cell lines (HEN-16, HEN-18, HEC-16, and HEC-18-1) were established by transfection of HPV 16 and 18 DNA into endocervical and ectocervical cells.(2) In vivo transplantation system revealed that immortalized cell lines derived from endocervical epithelium (HEN-16, HEN-18) formed higher grade lesion than those from ectocervical epithelium and their expression patte of cytokeratin coincided with that of adenocarcinoma of the cervix, which shows that these cell lines can be a model for a precursor lesion of cervical adenocarcinoma.(3) In the process of HPV-18-induced immortalization, it is revealed that precrisis culture contained more than 100 copies/cell of episomal HPV-18 DNA and no detectable integrated viral NDA,while the postcrisis cells contained a low copy number of only iontegrated viral genome. The northern blot patterns of E6-E7 and E2/E4 RNA were different between the cells before and after crisis. These results suggest that, although insufficient for tumorigenic transformation, viral DNA integration during crisis is associated with the establishment of an immortalized phenotype.(4) A tumorigenic cell line (HEC-18-1C) was established after treatment of immortalized HEC-18-1 cells with cigarette smoke condensate. Fomed tumor was invasive squamous cell carcinoma. The result suggests the role of cigarette smoke in the progression of HPV-initiated carcinogenesis of the cervix.

（1）通过将HPV 16和18 DNA转染为宫颈和邻里细胞。（2）在体内移植系统中，从较高的细胞中得出的细胞（Hen-16，Hen-16，Hen-16，Hen-16，-16，-16，），通过将HPV 16和18 DNA转染到室内和邻里细胞。 epithelium and their expression patte of cytokeratin coincided with that of adenocarcinoma of the cervix, which shows that these cell lines can be a model for a precursor lesion of cervical adenocarcinoma.(3) In the process of HPV-18-induced immortalization, it is revealed that precrisis culture contained more than 100 copies/cell of episomal HPV-18 DNA and no可检测的综合病毒NDA，而后危机细胞中只有低拷贝数的仅电离病毒基因组。危机前后细胞之间E6-E7和E2/E4 RNA的北印迹模式不同。这些结果表明，尽管不足以进行肿瘤性转化，但在危机期间的病毒DNA整合与建立永生的表型有关。（4）在用永生化的HEC-18-1细胞用香烟烟雾的烟气来治疗永生化的HEC-18-1细胞后，建立了肿瘤性细胞系（HEC-18-1C）。 FOMed肿瘤是侵入性鳞状细胞癌。结果表明，香烟烟雾在宫颈的HPV引起的致癌作用进展中的作用。

项目成果

Yokoyama,M.: "Human papillomavirus 18-immortalized endocervical cells with in vitro cytokeratin expression characteristics of" Obstetrics and Gynecology. 83. 197-204 (1994)

Yokoyama，M.：“具有体外细胞角蛋白表达特征的人乳头瘤病毒 18 永生化宫颈内膜细胞”妇产科。

横山正俊 他: "Human papillomavirus 18-immortalized endocervical cells with in vitro cytokeratin expression characteristicsof adenocarcinoma." Obstetrics & Gynecology. 83. 197-204 (1994)

Masatoshi Yokoyama 等人：“具有腺癌体外细胞角蛋白表达特征的人乳头瘤病毒 18 永生化宫颈管细胞。” 83. 197-204 (1994)

Yokoyama,M.: "Alterations in physical state and expression of human papillomavirus type 18 DNA following crisis and establishment" Virus Research. 37. 139-151 (1995)

Yokoyama,M.：“危机和建立后人乳头瘤病毒 18 型 DNA 的物理状态和表达的变化”病毒研究。

Nakao,Y.: "Malignant transformation of human fctocervical cells immortalized by HPV 18:in vitro model of carcinogenesis" Carcinogenesis. (in press). (1996)

Nakao,Y.：“HPV 18 永生化人类 fctocerv 细胞的恶性转化：致癌作用的体外模型”致癌作用。

Yokohama,M.: "Human papillomavirus 18-immortalized endocervical cells with in vitro cytokeratin expression characteristics of" Obstetrics and Gynecology. 83. 197-204 (1994)

Yokohama，M.：“具有体外细胞角蛋白表达特征的人乳头瘤病毒18永生化宫颈内膜细胞”妇产科。