Nuclear overexpression of the E2F3 transcription factor in human lung cancer.
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.
Cooper
Colin S
CS
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
Nicholson
Andrew G
AG
Foster
Christopher
C
Dodson
Andrew
A
Edwards
Sandra
S
Fletcher
Anne
A
Roe
Toby
T
Clark
Jeremy
J
Joshi
Anupam
A
Norman
Andrew
A
Feber
Andrew
A
Lin
Dongmei
D
Gao
Yanning
Y
Shipley
Janet
J
Cheng
Shu-Jun
SJ
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
D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human