Distinct mRNA, protein expression patterns and distribution of oestrogen receptors α and β in human primary breast cancer:: Correlation with proliferation marker Ki-67 and clinicopathological factors
Distinct mRNA, protein expression patterns and distribution of oestrogen receptors α and β in human primary breast cancer:: Correlation with proliferation marker Ki-67 and clinicopathological factors
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DOI：
10.1016/j.ejca.2005.09.010
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发表时间：
2005-12-01
影响因子：
8.4
通讯作者：
Wolczynski, S
中科院分区：
文献类型：
--
作者：
Jarzabek, K;Koda, M;Wolczynski, S
为了阐明雌激素受体 α 和 β（ER α、ER β）的分子特征，我们使用实时聚合酶链式反应 (RT-PCR)、蛋白质印迹分析和免疫组织化学 (IHC) 方法在 41 个原发性乳腺癌和周围组织中研究了 mRNA 和蛋白质水平的 ER α 和 ER β 表达。在所有分析的乳腺癌和正常匹配组织中均检测到 ER α mRNA 和 ER β mRNA。 ER α mRNA 水平比 ER β mRNA 水平表现出更大的多样性，并且 ER β 转录物数量范围远小于 ER α。在蛋白质水平上，ER α 或 ER β 阳性病例的百分比发生了变化。在蛋白质印迹分析中，70% 的研究肿瘤产生全长 65 kDa ER α 蛋白，并且 67% 的评估病例在 IHC 中呈阳性。通过蛋白质印迹法在 97% 的分析乳腺癌中检测到全长 57 kDa ER β 蛋白，而使用 IHC 检测发现 67% 的乳腺癌呈 ER β 阳性。 ER α 定位于细胞核，而在正常细胞和乳腺癌细胞中观察到 ER β 定位于细胞质和核周。 ER α（但不是 ER β）的量随着年龄的增长而增加。 ERα的表达与孕激素受体呈正相关，与增殖标志物Ki-67呈负相关。这些结果证实了之前的观察结果，即ERα蛋白表达的缺乏并不是由于ERα基因表达缺乏或ERα启动子甲基化所致，而是由于转录后或翻译后机制所致。我们的研究还表明，ER α 在乳腺癌中失调程度更高，因此 ER β 在肿瘤中受到更严格的调节。 (c) 2005 Elsevier Ltd. 保留所有权利。
To elucidate the molecular profile of oestrogen receptors alpha and beta (ER alpha, ER beta) we studied ER alpha and ER beta expression at the mRNA and protein levels using real-time polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemical (IHC) methods in 41 primary breast cancers and surrounding tissues. ER alpha mRNA and ER beta mRNA were detected in all of the breast cancer and normal matched tissues analysed. ER alpha mRNA levels showed greater diversity than ER beta mRNA levels and the range of amount of ER beta transcripts was far smaller than that of ER alpha. At the protein level, the percentage of ER alpha- or ER beta-positive cases changed. Seventy percent of the tumours studied produced full-length 65 kDa ER alpha protein in Western blot analysis and 67% of assessed cases were positive in IHC. Full-length 57 kDa ER beta protein was detected by Western blotting in 97% of analysed breast cancers, while 67% were ER beta-positive using IHC. ER alpha was localised in the nucleus, while cytoplasmic and perinuclear localisation of ER beta was observed in normal as well as in breast cancer cells. The amount of ER alpha (but not ER beta) increased with age. The expression of ER alpha correlated positively with progesterone receptor and negatively with proliferation marker Ki-67. These results confirm the previous observations that the lack of ER alpha protein expression is not due to lack of ER alpha gene expression or methylation of ER alpha promoter, but due to post-transcriptional or post-translational mechanisms. Our investigation also suggests that ER alpha is more dysregulated in breast cancer, and thereby ER beta is more tightly regulated in the tumour. (c) 2005 Elsevier Ltd. All rights reserved.