UbcH10 overexpression in human lung carcinomas and its correlation with EGFR and p53 mutational status

Eur J Cancer. 2013 Mar;49(5):1117-26. doi: 10.1016/j.ejca.2012.09.033. Epub 2012 Oct 24.

Abstract

Introduction: UbcH10 codes for the cancer related E2 Ubiquitin Conjugating Enzyme, an enzymatic molecule with a key role in the ubiquitin-proteasome pathway. Current studies have suggested a critical role of UbcH10 in a variety of malignancies, including human thyroid, breast, ovarian and colorectal carcinomas. The aim of this study has been to extend the analysis of UbcH10 expression to lung cancer. This neoplasia represents one of the leading cause of cancer mortality worldwide, and new tools for an accurate diagnosis/prognosis are needed.

Methods: The expression levels of UbcH10 were analysed in human non-small cell lung carcinoma (NSCLC) by quantitative RT-PCR and tissue microarray immunohistochemistry, and these values were correlated with the clinicopathological features of the patients affected by NSCLC.

Results: Our results demonstrate that UbcH10 is overexpressed in NSCLC compared to the normal lung tissue. Moreover, UbcH10 expression is significantly higher in squamous cell and large cell carcinomas than in adenocarcinomas, and directly and inversely correlated with the mutational status of p53 and EGFR, respectively. The suppression of UbcH10 expression by RNAi resulted in a drastic reduction of proliferation and migration abilities of lung carcinoma cell lines.

Conclusion: These results, taken together, indicate that UbcH10 overexpression has a critical role in lung carcinogenesis, and the evaluation of UbcH10 expression levels may be a new tool for the characterisation of NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • DNA Mutational Analysis
  • Epistasis, Genetic / genetics
  • Epistasis, Genetic / physiology
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, p53* / physiology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mutation* / physiology
  • Tissue Array Analysis
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Conjugating Enzymes / physiology

Substances

  • Biomarkers, Tumor
  • UBE2C protein, human
  • Ubiquitin-Conjugating Enzymes
  • EGFR protein, human
  • ErbB Receptors