HDAC6 expression is correlated with better survival in breast cancer
HDAC6 expression is correlated with better survival in breast cancer
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DOI：
10.1158/1078-0432.ccr-04-0455
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发表时间：
2004-10-15
影响因子：
11.5
通讯作者：
Iwase, H
中科院分区：
文献类型：
--
作者：
Zhang, ZH;Yamashita, H;Iwase, H
目的：组蛋白修饰可以改变染色质的结构和功能。组蛋白在体内的乙酰化是一个由组蛋白乙酰转移酶(HATS)和组蛋白脱乙酰酶(HDACs)控制的动态可逆过程。HDAC6是HDACs中唯一的异构体，利用基因芯片技术对HDAC6基因在MCF-7细胞中的表达谱进行了研究，结果表明HDAC6基因具有迟发性反应、雌激素诱导和上调作用。这导致我们假设HDAC6的表达水平与乳腺癌的转移潜能以及这些患者的预后之间存在联系。实验设计：在本研究中，采用实时定量逆转录-聚合酶链式反应分析了135例女性浸润性乳腺癌患者的HDAC6mRNA的表达水平。免疫组织化学方法检测HDAC6蛋白的表达。结果：在肿瘤直径小于2 cm、组织学分级低、雌激素受体α和孕激素受体阳性的乳腺癌患者中，HDAC6基因的表达水平显著升高。而HDAC6mRNA的表达与年龄、绝经状态、腋窝淋巴结转移等其他临床病理因素无关。就无病生存期而言，高水平表达HDAC6mRNA和蛋白的患者预后好于低水平表达的患者。但多因素分析未能显示HDAC6mRNA和蛋白是影响无瘤生存期和总生存期的独立预后因素。此外，HDAC6mRNA水平高的患者往往比低水平的患者对内分泌治疗更敏感。部分正常上皮细胞胞核和大多数癌细胞胞浆内可见特异的HDAC6染色。尽管绝经后乳腺癌患者HDAC6蛋白表达水平较高，但与其他临床病理因素无相关性。结论：HDAC6基因表达水平可作为乳腺癌内分泌反应的标志物，也可作为预后指标。关于HDAC6的表达和内分泌治疗反应之间的关系，有必要进行进一步的研究。
Purpose: The structure and function of chromatin can be altered by modifications to histone. Histone acetylation in vivo is a dynamic reversible process governed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC6 is a unique isoform among the HDACs, and a gene expression pattern study, with cDNA microarray in MCF-7 cells, showed the HDAC6 gene to be late responsive, estrogen induced, and up-regulated. This led us to hypothesize that there was a link between levels of HDAC6 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 HDAC6 mRNA expression was analyzed with quantitative real-time reverse transcription-PCR, in 135 female patients with invasive breast cancer. HDAC6 protein expression was also determined by immunohistochemistry. An association was sought between HDAC6 expression and various clinicopathologic factors.Results: HDAC6 mRNA was expressed at significantly higher levels in breast cancer patients with small tumors measuring less than 2 cm, with low histologic grade, and in estrogen receptor alpha- and progesterone receptor-positive tumors. By contrast, no relationship was found between HDAC6 mRNA expression and any of the other clinicopathologic factors, namely, age, menopausal status, and axillary lymph node involvement. Patients expressing high levels of HDAC6 mRNA and protein had a better prognosis than those expressing low levels, in terms of disease-free survival. However, multivariate analysis failed to show that HDAC6 mRNA and protein are an independent prognostic factors for disease-free survival and overall survival. Furthermore, the patients with high levels of HDAC6 mRNA tended to be more responsive to endocrine treatment than those with low levels. Specific HDAC6 staining was found in the nucleus of some normal epithelial cells and in the cytoplasm of the majority of cancer cells. Although postmenopausal patients showed higher HDAC6 protein expression, there were no relationship between protein expression and any other clinicopathologic factors.Conclusions: We conclude that the levels of HDAC6 mRNA expression may have potential both as a marker of endocrine responsiveness and also as a prognostic indicator in breast cancer. Additional investigations are warranted concerning the relationship between HDAC6 expression and response to endocrine therapy.