Umemura S, Shirane M, Takekoshi S, Kusakabe T, Itoh J, Egashira N, Tokuda Y, Mori K, Osamura Y R
Department of Pathology, Tokai University School of Medicine, Isehara, Japan.
Br J Cancer. 2009 Mar 10;100(5):764-71. doi: 10.1038/sj.bjc.6604900.
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.
本研究的目的是鉴定那些独立于雌激素受体（ER）或人表皮生长因子受体2（HER2）信号传导，而对乳腺癌细胞增殖或分化有作用的基因。一个寡核苷酸微阵列分析了来自ER(+)/HER2(-)、ER(+)/HER2(+)、ER(-)/HER2(+)和ER(-)/HER2(-)乳腺癌组织的40个肿瘤样本。定量逆转录聚合酶链反应检测到在ER阴性乳腺癌中一个细胞周期相关转录因子E2F-5的过表达，并且荧光原位杂交在57个乳腺癌样本中的5个（8.8%）检测到E2F-5的基因扩增。在E2F-5的DNA结合或DNA二聚化结构域未发现点突变。免疫组织化学显示，E2F-5阳性癌症与更高的Ki-67标记指数（59.5%，P = 0.001）和更高的组织学分级（P = 0.049）相关。E2F-5阳性癌症在ER(-)/孕激素受体（PgR）(-)/HER2(-)癌症样本中更常见（51.9%，P = 0.0049），并且在表现为基底样表型的乳腺癌样本中也更常见（56.0%，P = 0.0012）。E2F-5阳性癌症的淋巴结阴性患者的无病生存期短于E2F-5阴性癌症的患者。总之，我们首次鉴定出一群过表达细胞周期相关转录因子E2F-5的乳腺癌细胞。这种E2F-5阳性乳腺癌亚型与ER(-)/PgR(-)/HER2(-)状态、基底样表型以及更差的临床结局相关。
