Analysis and clinical application of ubiquitin system as a new target molecule in non-small cell lung cancer.

泛素系统作为非小细胞肺癌新靶分子的分析及临床应用

基本信息

批准号：
16591390
负责人：
SUZUKI Kazuya
金额：
$ 2.18万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591390/
关键词：
ubiquitin ligase Pirh2 p53 non small-cell lung cancer anticancer drug sensitivity test suppressor oncogene

项目摘要

Pirh2 was cloned as protein ARNIP which had a RING- finger domain to be connected to an androgen receptor. It is reported that this Pirh2 has ubiquitin ligase activity of p53, and leads p53 to degradation. Cancer growths will be accelerated if resolution of suppressor oncogene products such as p53 is enhanced by ubiquitin ligase activity of Pirh2. However, the roles of Pirh2 in clinical cases were not clear. Therefore we assayed expression of Pirh2 by real time RT-PCR using the non small-cell lung cancer tissues.Methods :The cDNA was composed by reverse transcriptase after getting a total RNA from a tissue. Primer was set to exon eight or nine to sandwich intron of a Pirh2 gene. Real time RT-PCR was performed using the primer mentioned above. In addition, degree of expression of Pirh2 and p27 was analysed by immunostaining.Results :In 13cases out of 20 adenocarcinoma, Pirh2 was more than double in cancer part tissues comparing with normal lung tissue. Well differentiated adenocarcinoma showed less expression of Pirh2 than moderately-poorly differentiated adenocarcinoma.In 8cases out of 9 squamous-cell carcinoma, Pirh2 was more than double in cancer tissues comparing with normal lung tissue.Manifestation of Pirh2 was confirmed in a lung cancer tissue by immunostaining.Discussion :High expression of Pirh2 was present in 70% of non small-cell lung cancer.It is thought that resolution of suppressor oncogene such as p27 and p53 is enhanced by ubiquitination through Pirh2 in non small-cell lung cancer. It was suggested that Pirh2 may contribute to the carcinogenesis or development of lung cancer.It seems that this research can develop concerning a correlation with clinical characteristics, prognosis, anticancer drug sensitivity test and so on.

将PIRH2克隆为蛋白Arnip，其环域可连接到雄激素受体。据报道，该PIRH2具有p53的泛素连接酶活性，并导致p53降解。如果PIRH2的泛素连接酶活性增强了抑制剂癌基产品（如p53）的分辨率，将加速癌症的生长。但是，PIRH2在临床病例中的作用尚不清楚。因此，我们使用非小细胞肺癌组织通过实时RT-PCR测定PIRH2的表达。方法：cDNA是通过从组织中获得总RNA后由逆转录酶组成的。底漆设置为piRH2基因的三明治内含子的外显子八或九。使用上述底漆进行实时RT-PCR。此外，通过免疫染色分析了PIRH2和P27的表达程度。分析：在20个腺癌中的13个例中，PIRH2在癌症部分组织中与正常肺组织相比是两倍多。良好分化的腺癌表现出PIRH2的表达较少，而不是中度偏差的腺癌。在9个鳞状细胞癌中，8个酶在癌症组织中与正常肺组织相比，PIRH2在癌症组织中是两倍以上是两倍以上。在肺癌组织中证实了PIRH2的表现。在肺癌组织中证实了70％。非小细胞性肺癌。人们认为，通过泛毒素通过PIRH2在非小细胞肺癌中的泛素化增强了抑制剂（例如p27和p53）的分辨率。有人提出，PIRH2可能有助于肺癌的致癌或发育。这项研究似乎可以与临床特征，预后，抗癌药物敏感性测试等有关。