ATBF1-a messenger RNA expression is correlated with better prognosis in breast cancer.
ATBF1-a messenger RNA expression is correlated with better prognosis in breast cancer.
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发表时间：
2005
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通讯作者：
Zhen-huan Zhang;H. Yamashita;T. Toyama;H. Sugiura;Y. Ando;K. Mita;M. Hamaguchi;M. Kawaguchi;Y. Miura;H. Iwase
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作者：
Zhen-huan Zhang;H. Yamashita;T. Toyama;H. Sugiura;Y. Ando;K. Mita;M. Hamaguchi;M. Kawaguchi;Y. Miura;H. Iwase
目的 AT 基序结合因子 1 (ATBF1) 基因首先通过与甲胎蛋白 (AFP) 基因的富含 AT 的增强子元件结合而被鉴定为该基因的抑制子。该基因位于染色体16q22.3-q23.1，在多种恶性肿瘤中观察到杂合性丢失，特别是在乳腺癌中。还发现，在高度恶性的产生AFP的胃癌细胞中，AFP的表达被ATBF1-A抑制。这使我们推测 ATBF1 表达水平与乳腺癌的转移潜力以及这些患者的预后之间存在联系。实验设计在本研究中，使用定量实时逆转录酶-PCR 分析了 153 名患有浸润性乳腺癌的女性患者的 ATBF1-A mRNA 表达水平。 ATBF1-A 蛋白表达也通过免疫组织化学测定了 90 例配对组织中的情况。寻找 ATBF1-A 表达与各种临床病理因素之间的关联。结果 ATBF1-A mRNA 在无腋窝淋巴结受累、肿瘤直径小于 2 cm 的小肿瘤以及雌激素受体 α 阳性肿瘤的乳腺癌患者中表达水平显着较高。相比之下，ATBF1-A mRNA 表达与 ATBF1-A 蛋白表达之间没有发现任何关系，并且 ATBF1-A 蛋白表达与任何其他临床病理因素之间也没有发现任何关系。表达高水平 ATBF1-A mRNA 的患者往往比表达低水平的患者预后更好。单变量和多变量预后分析表明 ATBF1-A mRNA 表达是无病生存的独立预后因素。结论在乳腺癌中，ATBF1-A mRNA 水平可作为淋巴结转移的预测指标。这项研究的结果还表明，ATBF1-A 基因表达可能既可以作为内分泌反应性的标志物，也可以作为乳腺癌进展的预后指标。
PURPOSE The AT motif-binding factor 1 (ATBF1) gene was first identified as a suppressor of the alpha-fetoprotein (AFP) gene through its binding to an AT-rich enhancer element of this gene. The gene is located at chromosome 16q22.3-q23.1 where loss of heterozygosity has been observed in various malignant tumors, especially in breast cancer. It was also found that in highly malignant AFP-producing gastric cancer cells the expression of AFP is inhibited by ATBF1-A. This led us to hypothesize that there was a link between levels of ATBF1 expression and the metastatic potential of breast cancer and also, therefore, the prognosis of these patients. EXPERIMENTAL DESIGN In the present study, the level of ATBF1-A mRNA expression was analyzed using quantitative real-time reverse transcriptase-PCR, in 153 female patients with invasive carcinoma of the breast. ATBF1-A protein expression was also determined by immunohistochemistry from available 90 cases of paired tissues. An association was sought between ATBF1-A expression and various clinicopathologic factors. RESULTS ATBF1-A mRNA was expressed at significantly higher levels in breast cancer patients with no axillary lymph node involvement, with small tumors measuring <2 cm and in estrogen receptor-alpha-positive tumors. By contrast, no relationship was found between ATBF1-A mRNA expression and ATBF1-A protein expression, and also no relationship was found between ATBF1-A protein expression and any of the other clinicopathologic factors. Patients expressing high levels of ATBF1-A mRNA tended to have a better prognosis than those expressing low levels. Univariate and multivariate prognostic analyses showed that ATBF1-A mRNA expression is an independent prognostic factor for disease-free survival. CONCLUSIONS In breast cancer, levels of ATBF1-A mRNA may serve as a predictive indicator of lymph node metastasis. The results of this study also imply that ATBF1-A gene expression may have potential both as a marker of endocrine responsiveness and also as a prognostic indicator for breast cancer progression.