Increased estrogen receptor βcx expression during mammary carcinogenesis
Increased estrogen receptor βcx expression during mammary carcinogenesis
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DOI：
10.1158/1078-0432.ccr-04-2298
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发表时间：
2005-05-01
影响因子：
11.5
通讯作者：
Rochefort, H
中科院分区：
文献类型：
--
作者：
Esslimani-Sahla, M;Kramar, A;Rochefort, H
在乳腺癌发生的早期阶段，蛋白质的显着变化的鉴定可能有助于了解其病理生理学和制定预防策略。比较了43例浸润性乳腺癌、39例邻近正常乳腺和26例导管原位癌（DCIS）中总雌激素受体β（ER β）蛋白及其羧基末端剪接变体ER β cx（或ER β 2）的表达。36例乳腺癌经放射配体结合试验ER阳性。使用先前验证的多克隆抗ER β 503 IgY和绵羊多克隆ER β cx抗体，通过福尔马林固定、石蜡包埋肿瘤的相邻切片的免疫组织化学进行分析。使用计算机图像分析仪在正常和癌上皮细胞的选定区域中定量核染色。ER β总表达在正常腺体中高，在DCIS中降低（P = 0.0004），从DCIS到浸润性肿瘤增加（P = 0.029）。相反，ER β cx表达在正常腺体中较低，在DCIS中显著增加（P = 0.0014），并且在ER α阳性和ER α阴性肿瘤中的浸润性癌中继续增加（P = 0.0027）。这是第一项研究显示，与邻近正常腺体相比，DCIS和浸润性乳腺癌中ER β cx变体蛋白显著增加。这与相同患者中总ER β水平的降低形成对比，并表明不同的机制来解释乳腺癌发生过程中的这些变化。它还表明ER β cx变体在致癌作用中的作用与野生型ER β 1的保护作用相反。
Identification of proteins that markedly vary during early steps of mammary carcinogenesis may help to understand its pathophysiology and to develop a prevention strategy. The expression of total estrogen receptor beta (ER beta) protein and of its COOH-terminally spliced variant ER beta cx (or ER beta 2) was compared in 43 invasive breast cancers and in 39 adjacent normal mammary glands and 26 ductal carcinoma in situ (DCIS). Thirty-six breast cancers were ER positive by radioligand binding assay. The analysis was done by immunohistochemistry on adjacent sections of formalin-fixed, paraffin-embedded tumors using polyclonal anti-ER beta 503 IgYand sheep polyclonal ER beta cx antibodies that were previously validated. Nuclear staining was quantified using a computerized image analyzer in selected areas of normal and cancer epithelial cells. Total ER beta expression was high in normal glands, decreased in DCIS (P = 0.0004), and increased from DCIS to invasive tumors (P = 0.029). In contrast, the ER beta cx expression was low in normal glands, increased significantly in DCIS (P = 0.0014), and continued to increase in invasive carcinomas (P = 0.0027) in both ER alpha-positive and ER alpha-negative tumors. This is the first study showing a significant increase of the ER beta cx variant protein in DCIS and invasive breast cancer compared with adjacent normal glands. This contrasts with the decrease of the total ER beta level in the same patients and indicates different mechanisms to explain these variations during mammary carcinogenesis. It also suggests a role of the ER beta cx variant in carcinogenesis opposite to the protective effect of the wild-type ER beta 1.