Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome

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.

E2F8 Contributes to Human Hepatocellular Carcinoma via Regulating Cell Proliferation

“…Besides, E2F1 was overexpressed in breast cancers (28), pancreatic ductal carcinoma (29), and gastric cancer (30). E2F5 was also overexpressed in breast cancer (31). In HCC, only both E2F1 and E2F3 were reported to be upregulated in cancerous tissues (14,15).…”

Immunohistochemical Ki67 labeling index has similar proliferation predictive power to various gene signatures in breast cancer

“…Details of the microarray analysis were described previously. (18) Total RNA was isolated by phenolchloroform extraction (Sepazol-I; Wako Pure Chemical Industries, Osaka, Japan) from 100-200 mg fresh frozen tissue. Extracted RNA was reverse transcribed to cDNA using T7-oligo-dT primer (Qiagen, Valencia, CA, USA) and converted to double-stranded DNA, which was used for synthesis of biotinlabeled cRNA using a MEGAscript Kit (Ambion, Austin, TX, USA).…”

miRNA-205 Suppresses Melanoma Cell Proliferation and Induces Senescence via Regulation of E2F1 Protein

“…E2F1 gene amplification and/or abnormalities in its expression have been reported in various tumor types, including melanoma (15,16). E2F5, another E2F family member, is an oncogenic cell cycle regulator demonstrated to be amplified or overexpressed in various tumors (17,18).…”