Estrogen receptor-α and C-ERBB-4 expression in breast carcinomas

Estrogen receptor-α and C-ERBB-4 expression in breast carcinomas
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DOI:
10.1007/s004280000392
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发表时间:
2001-07-01
期刊:
VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY
影响因子:
--
通讯作者:
Nesland, JM
Nesland, JM
中科院分区:
其他
文献类型:
--
作者:
Suo, ZH;Berner, HS;Nesland, JM

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乳腺癌中雌激素受体(ER)的存在对内分泌治疗的临床反应很重要。然而,ER激活后的细胞机制尚未完全了解。研究表明,ER的表达与c-erbB-4的表达相关。为了解决这个问题,103例乳腺癌样本进行了研究,使用逆转录聚合酶链反应(RT-PCR)分析后,应用微选择方法进行RNA分离。从20 μ m厚的冷冻切片中分离用于RT-PCR的总RNA。它们是从微选择区域中产生的。还对这103个肿瘤中的98个肿瘤的石蜡块进行了化学染色检查。ER-α之间的显著相关性。两种方法均检测到c-erbB-4 mRNA和蛋白表达。四分之一的肿瘤不表达ER-α。(22化学结合法、免疫组化法和RT-PCR法分别为24%和26%。大约一半的ER-α阴性肿瘤在mRNA和蛋白水平上均不表达c-erbB-4(RT-PCR为48%,免疫组化为46%,两种方法P=0.001)。内分泌治疗应答性乳腺癌细胞系MCF-7和T47-D对ER-α和c-erbB-4表达均呈阳性,而内分泌治疗无应答性乳腺癌细胞系MDA-MD-231和SK-BR-3则不呈阳性。因此,我们证实ER-α和c-erbB-4 mRNA和蛋白在乳腺癌中的表达之间的关联,表明c-erbB-4在雌激素信号转导中的作用。
The presence of estrogen receptors (ERs) in breast carcinomas is important for clinical response to endocrine therapy. However, the cellular mechanisms following ER activation are not fully understood. It has been indicated that expression of the ER is associated with the expression of c-erbB-4. To address this question, 103 breast carcinoma samples were studied using reverse transcriptase polymerase chain reaction (RT-PCR) analysis after application of a microselection method for RNA isolation. Total RNA for RT-PCR was isolated from 20-mum-thick frozen sections. which were made from microselected areas. Paraffin blocks from 98 of these 103 tumors were also immunohistochemically examined. Significant associations between ER-alpha. and c-erbB-4 mRNA and protein expressions were found in the present study with both methods. One-fourth of the tumors did not express ER-alpha. (22%, 24%, and 26% with chemical binding, immunohistochemistry, and RT-PCR, respectively). About one-half of the ER-alpha negative tumors did not express c-erbB-4 on both mRNA and protein levels (48% with RT-PCR and 46% with immunohistochemistry, P=0.001 for both methods). The endocrine therapy responsive breast cancer cell lines MCF-7 and T47-D were positive for both ER-alpha and c-erbB-4 expression, while the endocrine therapy nonresponsive breast cancer cell lines MDA-MD-231 and SK-BR-3 were not. Thus, we confirm the association between the expression of ER-alpha and c-erbB-4 mRNA and protein in breast carcinomas, indicating a role for c-erbB-4 in estrogen signal transduction.