title: Nuclear overexpression of the E2F3 transcription factor in human lung cancer.
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.
authors.affiliation: Section of Molecular Carcinogenesis, Male Urological Cancer Research Centre, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. colin.cooper@icr.ac.uk
authors.forename: Colin S
authors.initials: CS
authors.lastname: Cooper
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.forename: Christopher
authors.initials: C
authors.lastname: Foster
authors.forename: Andrew
authors.initials: A
authors.lastname: Dodson
authors.forename: Sandra
authors.initials: S
authors.lastname: Edwards
authors.forename: Anne
authors.initials: A
authors.lastname: Fletcher
authors.forename: Toby
authors.initials: T
authors.lastname: Roe
authors.forename: Jeremy
authors.initials: J
authors.lastname: Clark
authors.forename: Anupam
authors.initials: A
authors.lastname: Joshi
authors.forename: Andrew
authors.initials: A
authors.lastname: Norman
authors.forename: Andrew
authors.initials: A
authors.lastname: Feber
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lin
authors.forename: Yanning
authors.initials: Y
authors.lastname: Gao
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002276:Carcinoid Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human