Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors.
E2F transcription factors (E2F1 to 6) are central players in the control of animal cell proliferation as regulators of genes involved in cell cycle progression and in transformation. In this report, we have investigated the potential involvement of the E2F5 gene in tumorigenesis. We show that E2F5 can promote the formation of morphologically transformed foci in primary baby rat kidney cells (BRK) when it is overexpressed in the presence of its heterodimeric partner DP1 and activated RAS. This suggests that E2F5 behaves like a MYC-type cooperating oncogene in functional assays, prompting us to monitor potential amplifications of the E2F5 gene in primary human tumors. We mapped the human E2F5 gene to 8q21.1-21.3 equidistant from the MOS (8q12) and MYC (8q24) oncogenes. Since the long arm of chromosome 8 is frequently the site of increased gene copy number (ICN) in breast cancer, we screened 442 breast tumor DNAs for gains of E2F5, MOS, and MYC genes. The three genes showed ICN, albeit at variable incidence and levels of amplification, with the ICN of E2F5 occurring concomitantly with those of MOS and/or MYC in almost half of the cases. Moreover, a marked increase of the 2. 5-kb E2F5 transcript was also detected in some tumors and tumor cell lines. In conclusion, the evidence that sustained unregulated expression of E2F5 can cooperate with other oncogenes to promote cell transformation in functional assays, together with the detection of chromosomal amplifications and overexpressions of the E2F5 gene in breast tumors, provides the first indications that E2F5 deregulation may have a role in human tumor development.
Polanowska
J
J
Institut de Génétique Moléculaire, Montpellier, France.
Le Cam
L
L
Orsetti
B
B
Vallés
H
H
Fabbrizio
E
E
Fajas
L
L
Taviaux
S
S
Theillet
C
C
Sardet
C
C
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D050700:E2F5 Transcription Factor; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D009857:Oncogenes / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D050700:E2F5 Transcription Factor; C092558:E2F5 protein, human; C490489:E2f5 protein, rat; D014157:Transcription Factors