Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages in clear cell renal cell carcinoma

PLoS One. 2013 Sep 4;8(9):e73436. doi: 10.1371/journal.pone.0073436. eCollection 2013.

Abstract

Background: Transcription factor E2F1 exerts effects on many types of cancers. As an upstream regulator of a host of genes, E2F1 can trigger diverse aberrant transcription processes that may dominate malignancy. Clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinoma which displays high malignancy and has a shortage of biomarkers in clinics. Our study aimed to explore the function of E2F1 in ccRCC and its correlation with clinicopathological parameters.

Methodology/principle findings: Transcription factor E2F1 was mainly distributed in cancer cell nucleus and mRNA expression significantly increased in 72 cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (p<0.001). The protein expression was consistent with mRNA expression. Further analysis in 92 cases indicated that E2F1 mRNA level expression was associated with the tumor pathologic parameters embracing diameter, Fuhrman tumor grade, pT stage, TNM stage grouping and macrovascular infiltration (MAVI). These surgical specimens had high grade tumors accompanied with an elevated E2F1 expression. Moreover, E2F1 transfection was found to contribute significantly to cancer cell proliferation, migration and invasion in vitro.

Conclusions/significance: Overexpression of E2F1 may be a key event in the local and vascular infiltration of ccRCC indicated by the activation of matrix metalloproteinase (MMP) 2 and MMP9. These findings highlighted the implication of E2F1's function in the metastatic process. Furthermore, the clinical relevance of E2F1 in ccRCC pointed to a potential new therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinogenesis / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • E2F1 Transcription Factor / genetics*
  • E2F1 Transcription Factor / metabolism*
  • Extracellular Matrix / metabolism
  • Female
  • G1 Phase / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology*
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proteolysis
  • Retrospective Studies
  • S Phase / genetics
  • Up-Regulation

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9

Grants and funding

This work was supported by the National Nature Science Foundation (No. 81100483 and 30972982), Scientific Research Project for Health Industry (No.201002010), People’s Republic of China and the National High Technology Research and Development Program ("863"Program) of China: clinical exploratory application of LESS and NOTES in urology (2012AA02101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.