Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance.
Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance.
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DOI：
10.1002/cam4.41
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发表时间：
2012-12
期刊：
影响因子：
4
通讯作者：
Hayashi, Shin-ichi
中科院分区：
文献类型：
--
作者：
Gohno, Tatsuyuki;Seino, Yuko;Hanamura, Toru;Niwa, Toshifumi;Matsumoto, Mitsuyo;Yaegashi, Nobuo;Oba, Hanako;Kurosumi, Masafumi;Takei, Hiroyuki;Yamaguchi, Yuri;Hayashi, Shin-ichi
为了在个体水平上预测激素治疗的疗效，免疫组织化学方法用于分析经典分子生物标志物如雌激素受体（ER）、孕激素受体（PgR）和HER 2的表达。然而，目前的诊断标准对于不同病例的个体化来说并不完美。因此，需要建立更准确的诊断方法。在此之前，我们建立了一种新的方法，使ER的转录激活潜力分析在临床标本中使用腺病毒雌激素反应元件-绿色荧光蛋白（ERE-GFP）测定系统。使用这种方法，我们评估了62个原发性乳腺癌样本的ERE转录活性。在40%的样本中，我们观察到ER蛋白表达与ERE活性不一致。ERE活性与临床病理信息的比较显示，ERE活性与ER靶基因，PgR，而不是ER的蛋白质和mRNA的表达方面显着相关。此外，根据ERE活性对管腔A型乳腺癌样本进行亚组显示，在高ERE活性组中ERα mRNA表达与ER靶基因mRNA表达相关，而在低ERE活性组中则不相关。另一方面，低ERE活性组显示恶性肿瘤生物标志物Ki 67的mRNA表达显著较高，与5%患者的疾病复发相关。因此，这些数据表明ER表达并不总是与ER转录活性相关。因此，除了ER蛋白表达，测定作为ER功能标志物的ERE活性将有助于分析各种不同的乳腺癌病例和随后的治疗过程。
To predict the efficacy of hormonal therapy at the individual-level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element–green fluorescence protein (ERE-GFP) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR, rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of Luminal A-type breast cancer samples according to ERE activity revealed that ERα mRNA expression correlated with ER target gene mRNA expression in the high-, but not the low-, ERE-activity group. On the other hand, the low-ERE-activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment.
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影响因子：
64.5
作者：
Kouros-Mehr, Hosein;Slorach, Euan M.;Werb, Zena
通讯作者：
Werb, Zena
影响因子：
3.5
作者：
Inoue, A;Yoshida, N;Hayashi, S
通讯作者：
Hayashi, S
影响因子：
11.5
作者：
Badve, Sunil;Turbin, Dmitry;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
影响因子：
5.7
作者：
Yoshida, N;Omoto, Y;Hayashi, S
通讯作者：
Hayashi, S
影响因子：
6.2
作者：
Pujol, P;Daures, JP;Grenier, J
通讯作者：
Grenier, J