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Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors
Author(s) -
Polanowska Jolanta,
Le Cam Laurent,
Orsetti Béatrice,
Vallés Heléne,
Fabbrizio Eric,
Fajas Lluis,
Taviaux Sylvie,
Theillet Charles,
Sardet Claude
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200005)28:1<126::aid-gcc15>3.0.co;2-g
Subject(s) - carcinogenesis , e2f1 , biology , gene , oncogene , cancer research , e2f , transcription factor , tumor suppressor gene , cell cycle , genetics
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 E 2 F 5 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 DP 1 and activated RAS . This suggests that E 2 F 5 behaves like a MYC ‐type cooperating oncogene in functional assays, prompting us to monitor potential amplifications of the E 2 F 5 gene in primary human tumors. We mapped the human E 2 F 5 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 E 2 F 5, MOS , and MYC genes. The three genes showed ICN, albeit at variable incidence and levels of amplification, with the ICN of E 2 F 5 occurring concomitantly with those of MOS and/or MYC in almost half of the cases. Moreover, a marked increase of the 2.5‐kb E 2 F 5 transcript was also detected in some tumors and tumor cell lines. In conclusion, the evidence that sustained unregulated expression of E 2 F 5 can cooperate with other oncogenes to promote cell transformation in functional assays, together with the detection of chromosomal amplifications and overexpressions of the E 2 F 5 gene in breast tumors, provides the first indications that E 2 F 5 deregulation may have a role in human tumor development. Genes Chromosomes Cancer 28:126–130, 2000. © 2000 Wiley‐Liss, Inc.