Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance
Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance
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DOI：
10.1007/s10549-004-6457-4
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发表时间：
2005-05-01
影响因子：
3.8
通讯作者：
Stål, O
中科院分区：
文献类型：
--
作者：
Ahnström, M;Nordenskjöld, B;Stål, O
细胞周期蛋白D1在细胞周期G1期的调控中起重要作用。在乳腺上皮细胞中，细胞周期蛋白D1的表达通过雌激素受体和ErbB 2信号传导来调节。在这里，我们调查了230例乳腺癌患者中细胞周期蛋白D1的预后意义，随机接受他莫昔芬，CMF化疗和放疗。还分析了联合细胞周期蛋白D1和ErbB 2过表达的重要性。免疫组化结果显示，69例（29.8%）弱阳性，107例（46.5%）中度阳性，54例（23.7%）强阳性。ErbB 2的预后重要性是显着更大的肿瘤过表达细胞周期蛋白D1的患者比其他患者（p = 0.026）。在前一组中，ErbB 2过表达与复发风险增加（RR = 4.7; 95%CI，2.1-10.4）和乳腺癌死亡风险增加（RR = 5.4; 95%CI，2.3-12.6）密切相关。这一结果与证实细胞周期蛋白D1和ErbB 2在肿瘤发生中的联系的实验研究一致。在雌激素受体阳性患者中，中度细胞周期蛋白D1表达的患者从他莫昔芬治疗中明显获益（RR = 0.42; 95%CI，0.21-0.82），而弱或强表达的患者则没有。因此，细胞周期蛋白D1可能是他莫昔芬耐药的预测标志物。
Cyclin D1 plays an important role in the regulation of the G1 phase in the cell cycle. In mammary epithelial cells the expression of cyclin D1 is regulated through the oestrogen receptor and via ErbB2 signalling. Here we investigated the prognostic significance of cyclin D1 among 230 breast cancer patients randomised for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107 (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The prognostic importance of ErbB2 was significantly greater for patients whose tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the former group, ErbB2 overexpression was strongly associated with increased risk of recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95% CI, 2.3-12.6). This result is in accordance with experimental studies demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen receptor positive patients, those with moderate cyclin D1 expression significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82) whereas those with weak or strong expression did not. Therefore cyclin D1 might be a predictive marker for tamoxifen resistance.