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Overexpression of E2F-5 Correlates with a Pathological Basal Phenotype and a Worse Clinical Outcome

Overview
Journal Br J Cancer
Specialty Oncology
Date 2009 Mar 5
PMID 19259095
Citations 29
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Abstract

The purpose of the present study is to identify genes that contribute to cell proliferation or differentiation of breast cancers independent of signalling through the oestrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2). An oligonucleotide microarray assayed 40 tumour samples from ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) breast cancer tissues. Quantitative reverse transcriptase PCR detected overexpression of a cell cycle-related transcription factor, E2F-5, in ER-negative breast cancers, and fluorescence in situ hybridisation detected gene amplification of E2F-5 in 5 out of 57 (8.8%) breast cancer samples. No point mutations were found in the DNA-binding or DNA-dimerisation domain of E2F-5. Immunohistochemically, E2F-5-positive cancers correlated with a higher Ki-67 labelling index (59.5%, P=0.001) and higher histological grades (P=0.049). E2F-5-positive cancers were found more frequently in ER(-)/progesterone receptor (PgR)(-)/HER2(-) cancer samples (51.9%, P=0.0049) and in breast cancer samples exhibiting a basal phenotype (56.0%, P=0.0012). Disease-free survival in node-negative patients with E2F-5-positive cancers was shorter than for patients with E2F-5-negative cancers. In conclusion, we identify, for the first time, a population of breast cancer cells that overexpress the cell cycle-related transcription factor, E2F-5. This E2F-5-positive breast cancer subtype was associated with an ER(-)/PgR(-)/HER2(-) status, a basal phenotype, and a worse clinical outcome.

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References
1.
Trimarchi J, Fairchild B, VERONA R, Moberg K, Andon N, Lees J . E2F-6, a member of the E2F family that can behave as a transcriptional repressor. Proc Natl Acad Sci U S A. 1998; 95(6):2850-5. PMC: 19658. DOI: 10.1073/pnas.95.6.2850. View

2.
Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View

3.
Campanero M, Armstrong M, Flemington E . Distinct cellular factors regulate the c-myb promoter through its E2F element. Mol Cell Biol. 1999; 19(12):8442-50. PMC: 84947. DOI: 10.1128/MCB.19.12.8442. View

4.
Lees J, Saito M, Vidal M, Valentine M, Look T, Harlow E . The retinoblastoma protein binds to a family of E2F transcription factors. Mol Cell Biol. 1993; 13(12):7813-25. PMC: 364853. DOI: 10.1128/mcb.13.12.7813-7825.1993. View

5.
Gaubatz S, Lindeman G, Ishida S, Jakoi L, Nevins J, Livingston D . E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Mol Cell. 2000; 6(3):729-35. DOI: 10.1016/s1097-2765(00)00071-x. View