Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer.
Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer.
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DOI：
10.1038/ncomms3175
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发表时间：
2013
影响因子：
16.6
通讯作者：
Lehtio, Janne
中科院分区：
文献类型：
--
作者：
Johansson, Henrik J.;Sanchez, Betzabe C.;Mundt, Filip;Forshed, Jenny;Kovacs, Aniko;Panizza, Elena;Hultin-Rosenberg, Lina;Lundgren, Bo;Martens, Ulf;Mathe, Gyongyver;Yakhini, Zohar;Helou, Khalil;Krawiec, Kamilla;Kanter, Lena;Hjerpe, Anders;Stal, Olle;Linderholm, Barbro K.;Lehtio, Janne
大约三分之一的雌激素受体α阳性乳腺癌患者接受他莫昔芬治疗后复发。在这里，我们确定核受体视黄酸受体α作为他莫昔芬耐药的标志物。使用定量质谱为基础的蛋白质组学，我们表明，视黄酸受体α蛋白质网络和水平不同的他莫昔芬敏感（MCF7）和他莫昔芬耐药（LCC 2）细胞系。高的肿瘤内维甲酸受体α蛋白水平也与雌激素受体α阳性乳腺癌患者单独接受他莫昔芬辅助治疗的无复发生存率降低相关。类似的视黄酸受体α表达模式在一个可比较的独立患者队列中观察到。雌激素受体α和视黄酸受体α配体筛选表明，与MCF7细胞相比，他莫昔芬耐药LCC 2细胞对视黄酸受体α配体的敏感性增加，对雌激素受体α配体的敏感性降低。我们的数据表明，视黄酸受体α可能是一个新的治疗靶点和雌激素受体α阳性乳腺癌患者辅助他莫昔芬治疗的预测因素。 许多乳腺癌患者对三苯氧胺产生耐药性并复发。Johansson等人将核受体视黄酸受体α（RARA）鉴定为他莫昔芬耐药的标志物，并表明RARA表达与患者的无复发生存率呈负相关。
About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen. Many patients with breast cancer develop resistance to the drug tamoxifen and relapse. Here Johansson et al. identify the nuclear receptor retinoic acid receptor alpha (RARA) as a marker of tamoxifen resistance and show that RARA expression correlates negatively with relapse-free survival of patients.
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影响因子：
9.9
作者：
Hua, Sujun;Kallen, Caleb B.;Dhar, Ruby;Baquero, Maria T.;Mason, Christopher E.;Russell, Beth A.;Shah, Parantu K.;Liu, Jiang;Khramtsov, Andrey;Tretiakova, Maria S.;Krausz, Thomas N.;Olopade, Olufunmilayo I.;Rimm, David L.;White, Kevin P.
通讯作者：
White, Kevin P.
影响因子：
3.4
作者：
Eriksson, Hanna;Lengqvist, Johan;Jakobsson, Per-Johan
通讯作者：
Jakobsson, Per-Johan
影响因子：
10.3
作者：
Colditz, GA
通讯作者：
Colditz, GA
影响因子：
--
作者：
Germain, Pierre;Gaudon, Claudine;Gronemeyer, Hinrich
通讯作者：
Gronemeyer, Hinrich
DOI：
10.1007/s00432-008-0354-x
发表时间：
2008-08-01
影响因子：
3.6
作者：
Fan, Jiang;Yin, Wen-Jin;Shao, Zhi-Min
通讯作者：
Shao, Zhi-Min