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

Our plain-English summary of 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, by C. Xu, C. Wu, Y. Xia, et al (PloS One, 2013).

The study

• Authors: C. Xu, C. Wu, Y. Xia, Z. Zhong, X. Liu, J. Xu, F. Cui, B. Chen, O.D. Røe, A. Li, Y. Chen
• Journal: PloS One
• Published: 2013;8(8):e68837
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study examined the Wilms' tumor gene (WT1) in non-small cell lung cancer (NSCLC). The authors compared 85 pairs of NSCLC and corresponding adjacent tissues from patients operated on at the First Affiliated Hospital of Nanjing Medical University between December 2010 and April 2011, using immunohistochemistry and real-time PCR, and reported significantly higher WT1 protein staining (p less than 0.05) and WT1 mRNA (p less than 0.001) in tumour tissue. In three NSCLC cell lines (A549, H1299, H1650), lentiviral overexpression of WT1 increased cell viability while WT1-shRNA knockdown reduced it; flow cytometry showed a higher proportion of cells in S-phase with WT1 overexpression and a lower proportion with knockdown, and Western blotting showed Cyclin D1 and p-pRb increased with WT1 overexpression and reduced with knockdown. No effect of WT1 on apoptosis was found. In Balb/c nu/nu mouse xenografts, WT1-overexpressing cells produced larger tumours and WT1-shRNA cells smaller tumours. Mesothelioma is mentioned as background, in the abstract and introduction, but was not studied here.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study combining analysis of surgical tumour specimens, NSCLC cell line experiments with lentiviral overexpression and shRNA knockdown, and a mouse xenograft experiment
• Who was studied: 85 consecutive de novo NSCLC patients with paired adjacent tissue (Nanjing, China, December 2010 to April 2011); cell lines A549, H1299, H1650 and 293T; 90 Balb/c nu/nu mice in xenograft experiments
• Exposure: Not an exposure study: the manipulated factor was WT1 expression, raised by lentiviral pLV-GFP-WT1 and lowered by pLL3.7-WT1-shRNA in NSCLC cells
• Main results:
  • WT1 mRNA was significantly higher in NSCLC specimens than in adjacent tissues (p less than 0.001); WT1 staining was also higher (p less than 0.05)
  • In the three NSCLC cell lines, WT1 overexpression increased cell viability and WT1 knockdown reduced it (CCK-8 assay)
  • The WT1 overexpression group had a higher percentage of cells in S-phase than control; the WT1 knockdown group lower
  • Cyclin D1 and p-pRb protein increased in WT1-overexpressing cells and decreased in WT1 down-regulated cells
  • No effect of WT1 on apoptosis of NSCLC cells was detected
  • In mice, tumour volume increased with pLV-GFP-WT1 transduced cells and decreased with pLL3.7-WT1-shRNA cells
  • In xenograft tumours, Cyclin D1 and p-pRb were higher in WT1-overexpressing tissue than in WT1 down-regulated tissue, while p-STAT3 (S727) was overexpressed in both
• The authors' conclusion: The authors concluded that WT1 expression was higher in NSCLC than in adjacent tissue, that WT1 promoted proliferation in vitro and in vivo, and that it plays an oncogenic role by up-regulating Cyclin D1 and p-pRb, potentially serving as a therapeutic target
• Limitations the authors state:
  • The authors stated the reason for the difference from other reports on WT1 and apoptosis/Bcl-2L remains unknown and needs further elucidation
  • The authors noted that whether WT1 is associated with STAT3 phosphorylation has not been investigated
  • The authors stated further research is needed on WT1's function in tumour invasion and metastasis
  • Not all injected mice developed tumours in the knockdown groups

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Non-Small Cell Lung Cancer, Tumor Suppressor Gene, Mesothelioma, Lung Cancer, Carcinogenesis.

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