Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome.
Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome.
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DOI：
10.1038/sj.bjc.6604900
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发表时间：
2009-03-10
影响因子：
8.8
通讯作者：
Osamura, Y. R.
中科院分区：
文献类型：
--
作者：
Umemura, S.;Shirane, M.;Takekoshi, S.;Kusakabe, T.;Itoh, J.;Egashira, N.;Tokuda, Y.;Mori, K.;Osamura, Y. R.
本研究的目的是通过雌激素受体(ER)或人表皮生长因子受体2(HER2)识别与乳腺癌细胞增殖或分化有关的不依赖于信号的基因。用寡核苷酸芯片检测了ER(+)/HER2(−)、ER(+)/HER2(+)、ER(−)/HER2(+)和ER(−)/HER2(−)乳腺癌组织中的40例肿瘤标本。定量逆转录聚合酶链式反应检测到ER阴性乳腺癌中细胞周期相关转录因子E2F-5的过度表达，荧光原位杂交检测到57例乳腺癌标本中有5例E2F-5基因扩增(8.8%)。在E2F-5的DNA结合区或DNA二聚区未发现点突变。免疫组织化学显示，E2F-5阳性与Ki-67标记指数高(59.5%，P=0.001)和组织学分级高(P=0.049)相关。E2F-5在ER(−)/孕激素受体(−)/HER2(−)癌组织中阳性率为51.9%(P=0.0049)，在基本表型乳腺癌组织中阳性率为56.0%(P=0.0012)。淋巴结阴性的E2F-5阳性癌症患者的无瘤生存期比E2F-5阴性的癌症患者短。总之，我们首次确定了一组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阳性的乳腺癌亚型与ER(−)/PgR(−)/HER2(−)状态、基本表型和较差的临床结果相关。
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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影响因子：
45.3
作者：
Cobleigh, MA;Vogel, CL;Slamon, DJ
通讯作者：
Slamon, DJ
影响因子：
10.5
作者：
Lukas, J;Herzinger, T;Bartek, J
通讯作者：
Bartek, J
影响因子：
4.8
作者：
Delmas, C;Manenti, S;Darbon, JM
通讯作者：
Darbon, JM
影响因子：
10.5
作者：
Lindeman, GJ;Dagnino, L;Livingston, DM
通讯作者：
Livingston, DM
影响因子：
8
作者：
Macaluso, M;Cinti, C;Giordano, A
通讯作者：
Giordano, A