Nuclear overexpression of the E2F3 transcription factor in human lung cancer

Lung Cancer. 2006 Nov;54(2):155-62. doi: 10.1016/j.lungcan.2006.07.005. Epub 2006 Aug 30.

Abstract

Background: The E2F3 transcription factor has an established role in controlling cell cycle progression. In previous studies we have provided evidence that nuclear E2F3 overexpression represents a mechanism that drives the development of human bladder cancer and that determines aggressiveness in human prostate cancer. We have proposed a model in which E2F3 overexpression co-operates with removal of the E2F inhibitor pRB to facilitate cancer development. Since small cell lung cancers (SCLC) have one of the highest reported frequencies of functional abnormalities in the pRB protein (90%) of any human cancer, we wish to assess to what extent E2F3 would be overexpressed in this and other classes of human lung cancer.

Methods: Immunohistochemical techniques were used to assess the E2F3 status in 428 samples of lung cancers, lung carcinoids, normal bronchial epithelium and normal lung tissue.

Results: E2F3 is overexpressed in 55-70% of squamous cell carcinomas and 79% of adenocarcinomas of the lung. In addition very high level expression of nuclear E2F3 is found in almost all small cell lung cancers analysed. When considered together with published data our observations indicate that co-operation between pRB functional knockouts and E2F3 overexpression may represent a mechanism of development of SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Carcinoid Tumor / genetics
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / pathology
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Nucleus / metabolism
  • E2F3 Transcription Factor / genetics
  • E2F3 Transcription Factor / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Genes, Retinoblastoma
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Oligonucleotide Array Sequence Analysis

Substances

  • E2F3 Transcription Factor
  • E2F3 protein, human