Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer--overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression.
Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer--overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression.
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DOI：
10.1186/1471-2407-13-215
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发表时间：
2013-04-30
期刊：
影响因子：
3.8
通讯作者：
Denkert C
中科院分区：
文献类型：
--
作者：
Müller BM;Jana L;Kasajima A;Lehmann A;Prinzler J;Budczies J;Winzer KJ;Dietel M;Weichert W;Denkert C
在乳腺癌中，表观遗传改变包括组蛋白乙酰化状态的修饰在癌发生中的作用在过去几年中一直是重要的研究焦点。组蛋白的脱乙酰化增加导致细胞增殖、细胞迁移、血管生成和侵袭增加。1类组蛋白去乙酰化酶（HDAC）似乎是最重要的癌变过程中。应用免疫组化组织芯片技术检测238例原发性乳腺癌组织中HDAC 1、2和3的表达。我们分析了核染色强度（阴性、弱、中等、强）以及阳性肿瘤细胞的百分比，并计算免疫反应性评分（0-12）。表达与临床病理参数和患者生存相关。在该队列中，我们发现HDAC 1、HDAC 2和HDAC 3的差异阳性表达。HDAC 2和HDAC 3表达在分化较低的肿瘤中显著较高：HDAC 2（n=207），p<0.001和HDAC 3（n=220），p<0.001，并且与阴性激素受体状态相关：HDAC 2（n=206），p=0.02和HDAC 3（n=219），p=0.04。此外，HDAC 2高表达与HER 2过表达（n=203，p=0.005）和淋巴结转移（n=200，p=0.04）显著相关。HDAC 1在激素受体阳性肿瘤中高度表达（n=203; p<0.001）。总之，我们的研究结果表明，1类HDAC同工酶1，2和3在乳腺癌中的差异表达。HDAC 2和HDAC 3在具有更侵袭性肿瘤类型特征的肿瘤亚组中强烈表达。
In breast cancer, the role of epigenetic alterations including modifications of the acetylation status of histones in carcinogenesis has been an important research focus during the last years. An increased deacetylation of histones leads to increased cell proliferation, cell migration, angiogenesis and invasion. Class 1 histone deacetylases (HDAC) seem to be most important during carcinogenesis. The immunhistochemical expression of HDAC1, 2 and 3 was analyzed on tissue microarrays (TMAs) from 238 patients with primary breast cancer. We analyzed the nuclear staining intensity (negative, weak, moderate, strong) as well as the percentage of positive tumor cells and calculated the immunoreactivity score (0–12). Expression was correlated with clinicopathological parameters and patient survival. In this cohort, we found a differential positive expression of HDAC1, HDAC2 and HDAC3. HDAC2 and HDAC3 expression was significantly higher in less differentiated tumors: HDAC2 (n=207), p<0.001 and HDAC3 (n=220), p<0.001 and correlated with negative hormone receptor status: HDAC2 (n=206), p=0.02 and HDAC3 (n=219), p=0.04. Additionally, a high HDAC2 expression was significantly associated with an overexpression of HER2 (n=203, p=0.005) and the presence of nodal metastasis (n=200, p=0.04). HDAC1 was highly expressed in hormone receptor positive tumors (n=203; p<0.001). As a conclusion, our results show that the class-1 HDAC isoenzymes 1, 2 and 3 are differentially expressed in breast cancer. HDAC2 and HDAC3 are strongly expressed in subgroups of tumor with features of a more aggressive tumor type.
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影响因子：
1.6
作者：
Schneider, Gunter;Kramer, Oliver H;Saur, Dieter
通讯作者：
Saur, Dieter
DOI：
10.1158/1078-0432.ccr-08-2319
发表时间：
2009-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Suzuki J;Chen YY;Scott GK;Devries S;Chin K;Benz CC;Waldman FM;Hwang ES
通讯作者：
Hwang ES
影响因子：
11.2
作者：
Bicaku, Elona;Marchion, Douglas C.;Munster, Pamela N.
通讯作者：
Munster, Pamela N.
影响因子：
4.1
作者：
Fortunati, N.;Bertino, S.;Boccuzzi, G.
通讯作者：
Boccuzzi, G.
影响因子：
11.5
作者：
Bali, P;Pranpat, M;Bhalla, K
通讯作者：
Bhalla, K