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首页> 外文期刊>Oncogene >Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer
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Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer

机译：CCND1和PAK1的扩增可预测绝经后乳腺癌的复发和他莫昔芬耐药

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The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1, assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1-amplified tumors, indicating coamplification (PP=0.025). When response to tamoxifen treatment was analysed, patients with PAK1 amplification showed decreased benefit from the drug (ER+; relative risk ratio (RR)=1.62; 95% confidence interval (CI), 0.47–5.55) compared to patients without amplification (ER+; RR=0.53; 95% CI, 0.32–0.88). This was not evident for CCND1 amplification. We show that PAK1 may be a predictor of tamoxifen resistance and furthermore, we do not discard PAK1 as a potential candidate oncogene in the 11q13 amplicon. In addition, we show that high pak1 protein levels may predict tamoxifen insensitivity.
机译：在所有乳腺肿瘤的约15％中11q13区被扩增。 cyclin D1基因（CCND1）和p-21激活激酶1（PAK1）基因位于该区域。这两个基因编码的蛋白质均能激活雌激素受体（ER），从而导致CCND1和其他ER反应性基因转录。在这里，我们调查了CCND1和PAK1基因扩增在绝经后乳腺癌患者中的随机性和他莫昔芬治疗或无辅助治疗的预后和治疗预测作用。通过实时PCR评估，CCND1和PAK1的扩增分别达到12.5％和9.3％。在37％的CCND1扩增肿瘤中可见PAK1扩增，表明存在共扩增（PP = 0.025）。分析对他莫昔芬治疗的反应后，与未扩增的患者（ER +）相比，PAK1扩增的患者显示出该药的获益降低（ER +;相对风险比（RR）= 1.62; 95％置信区间（CI），0.47-5.55） ; RR = 0.53; 95％CI，0.32-0.88）。对于CCND1扩增，这并不明显。我们表明，PAK1可能是他莫昔芬耐药性的预测因子，此外，我们并未将PAK1丢弃为11q13扩增子中潜在的候选癌基因。此外，我们显示高pak1蛋白水平可能预示他莫昔芬不敏感。

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