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.
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.
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Soochow, Jiangsu, China.
Caihua
C
Xu
Chen
C
Wu
Yang
Y
Xia
Zhaopeng
Z
Zhong
Xiang
X
Liu
Jing
J
Xu
Fei
F
Cui
Bin
B
Chen
Oluf Dimitri
OD
Røe
Aihong
A
Li
Yijiang
Y
Chen
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
D010750:Phosphoproteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D050796:STAT3 Transcription Factor; D025721:WT1 Proteins; D019938:Cyclin D1