WT1 Promotes Cell Proliferation in Non-Small Cell Lung Cancer Cell Lines Through Up-Regulating Cyclin D1 and p-pRb In Vitro and In Vivo

被引:35
作者
Xu, Caihua [1 ]
Wu, Chen [2 ]
Xia, Yang [2 ]
Zhong, Zhaopeng [2 ]
Liu, Xiang [2 ]
Xu, Jing [2 ]
Cui, Fei [3 ]
Chen, Bin [4 ]
Roe, Oluf Dimitri [5 ]
Li, Aihong [6 ]
Chen, Yijiang [2 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Cardiovasc Surg, Suzhou, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Thorac & Cardiovasc Surg, Nanjing, Jiangsu, Peoples R China
[3] Guangzhou Med Univ, Affiliated Hosp 1, Dept Thorac & Cardiovasc Surg, Guangzhou, Guangdong, Peoples R China
[4] Wuxi 2 Peoples Hosp, Dept Thorac & Cardiovasc Surg, Wuxi, Jiangsu, Peoples R China
[5] Norwegian Univ Sci & Technol NTNU, Fac Med, Dept Canc Res & Mol Med IKM, Trondheim, Norway
[6] Umea Univ, Clin Chem, Dept Med Biosci, Umea, Sweden
基金
中国国家自然科学基金;
关键词
TUMOR-SUPPRESSOR; S-PHASE; PROTEIN; GENE; EXPRESSION; WILMS-TUMOR-1; ONCOGENESIS; ACTIVATION; APOPTOSIS; MOUSE;
D O I
10.1371/journal.pone.0068837
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Wilms' tumor suppressor gene (WT1) has been identified as an oncogene in many malignant diseases such as leukaemia, breast cancer, mesothelioma and lung cancer. However, the role of WT1 in non-small-cell lung cancer (NSCLC) carcinogenesis remains unclear. In this study, we compared WT1 mRNA levels in NSCLC tissues with paired corresponding adjacent tissues and identified significantly higher expression in NSCLC specimens. Cell proliferation of three NSCLC cell lines positively correlated with WT1 expression; moreover, these associations were identified in both cell lines and a xenograft mouse model. Furthermore, we demonstrated that up-regulation of Cyclin D1 and the phosphorylated retinoblastoma protein (p-pRb) was mechanistically related to WT1 accelerating cells to S-phase. In conclusion, our findings demonstrated that WT1 is an oncogene and promotes NSCLC cell proliferation by up-regulating Cyclin D1 and p-pRb expression.
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页数:10
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