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

PLoS One. 2013 Aug 1;8(8):e68837. doi: 10.1371/journal.pone.0068837. Print 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Cyclin D1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Phosphoproteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinoblastoma Protein / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Transcriptional Activation
  • Up-Regulation*
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism*

Substances

  • Phosphoproteins
  • RNA, Messenger
  • Retinoblastoma Protein
  • STAT3 Transcription Factor
  • WT1 Proteins
  • Cyclin D1

Grants and funding

This work was supported in part by the National Natural Science Foundation of China [81170158] (http://www.nsfc.gov.cn/Portal0/default152.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.