Y-box binding protein, YB-1, as a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer.
Y-box binding protein, YB-1, as a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer.
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DOI：
10.3892/ijo.26.3.607
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发表时间：
2005-03
影响因子：
5.2
通讯作者：
Jingxiang Huang;P. Tan;K. Li;Ken Matsumoto;M. Tsujimoto;B. Bay
中科院分区：
文献类型：
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作者：
Jingxiang Huang;P. Tan;K. Li;Ken Matsumoto;M. Tsujimoto;B. Bay
Y盒结合蛋白1（YB-1）通过转录和翻译调节基因表达。YB-1已被证明与P-糖蛋白（Pgp）的上调有关，P-糖蛋白是一种参与多药耐药的ATP结合转运蛋白。在这项研究中，我们确定了YB-1的预后意义及其与Pgp在乳腺癌患者中的关系。应用免疫组织化学方法检测了99例和57例浸润性导管乳腺癌中YB-1和Pgp的表达，并与临床病理参数和辅助化疗方案进行了相关性分析。通过将纯化的重组鸡YB-1蛋白注射到兔中来制备YB-1蛋白的抗体。还通过使用共振识别模型（RRM）的计算方法评估YB-1和Pgp之间的关系。我们发现，乳腺肿瘤雌激素受体阴性和淋巴结阳性与高YB-1表达（P=0.017）。在未接受辅助化疗的患者中，YB-1表达较低的乳腺癌复发风险降低（P=0.034），表明乳腺癌中高水平的YB-1表达与肿瘤侵袭性相关。我们能够使用基于计算机的RRM证明YB-1和Pgp之间的直接相互作用。有趣的是，我们发现，与环磷酰胺/甲氨蝶呤/5-氟尿嘧啶方案的患者相比，接受含有蒽环类药物（Pgp底物）的化疗方案并随后发生复发的患者具有更高的YB-1评分（P=0.024）。YB-1在乳腺癌中的表达可能是化疗耐药的潜在标志物，并可能有助于选择合适的乳腺癌辅助化疗方案。
The Y-box binding protein 1 (YB-1) regulates gene expression through transcription and translation. YB-1 has been shown to be associated with up-regulation of P-glycoprotein (Pgp), an ATP-binding transporter involved in multi-drug resistance. In this study, we determined the prognostic significance of YB-1 and its relationship with Pgp in patients with breast cancer. YB-1 and Pgp expression were evaluated by immunohistochemistry in resected specimens of infiltrative ductal breast cancers from 99 patients and 57 patients respectively and correlated with clinicopathological parameters and adjuvant chemotherapy regimes. The antibody for the YB-1 protein was prepared by injecting a rabbit with a purified recombinant chicken YB1 protein. The relationship between YB-1 and Pgp was also evaluated by a computational approach using the Resonant Recognition Model (RRM). We found that breast tumors which were both estrogen receptor-negative and lymph node positive were associated with high YB-1 expression (P=0.017). In patients who did not receive adjuvant chemotherapy, recurrence risk was reduced in breast cancers having lower YB-1 expression (P=0.034), suggesting that high levels of YB-1 expression in breast cancer is associated with tumor aggressiveness. We were able to demonstrate a direct interaction between YB-1 and Pgp using the computer-based RRM. Interestingly, we found that patients who were on a chemotherapy regime which contained an anthracycline (a Pgp substrate) and subsequently developed recurrence, had a higher YB-1 score compared to patients on the Cyclophosphamide/Methotrexate/5-Fluorouracil regime (P=0.024). YB-1 expression in breast cancer may be a potential marker of chemoresistance and could possibly aid in selection of the appropriate adjuvant chemotherapy regime for breast cancers.