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新型雌激素受体共激活因子PELP1/MNAR基因及雌激素受体β在涎腺导管腺癌中的表达:潜在治疗靶点

Novel estrogen receptor coactivator PELP1/MNAR gene and ERbeta expression in salivary duct adenocarcinoma: potential therapeutic targets.

作者信息

Vadlamudi Ratna K, Balasenthil Seetharaman, Sahin Aysegul A, Kies Merrill, Weber Randal S, Kumar Rakesh, El-Naggar Adel K

机构信息

Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Hum Pathol. 2005 Jun;36(6):670-5. doi: 10.1016/j.humpath.2005.03.016.

DOI:10.1016/j.humpath.2005.03.016
PMID:16021574
Abstract

Salivary duct carcinoma (SDC) is a high-grade neoplasm with marked morphological resemblance to mammary duct carcinoma. The novel estrogen receptor (ER)-interacting protein and the proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), also called the modulator of nongenomic activity of ER ( MNAR ), have been shown to activate steroid hormone receptors in mammary carcinomas by nongenomic and genomic mechanisms. The expression and the relationship of this gene to the ER status in SDCs are unknown. We investigated the differential expression of the PELP1 / MNAR and the ERs alpha and beta proteins in SDCs, using Western blotting and immunohistochemistry. Western blot analysis of 7 paired normal and tumor specimens showed increased expression of PELP1 / MNAR and ER beta in 3 and 4 of the SDCs, respectively. No detectable expression of ER alpha in any normal or SDC specimens was noted. Immunohistochemical staining performed on 70 SDCs revealed strong expression of PELP1 / MNAR in 51 (73%) and ER beta in 52 (74%) tumors. PELP1 / MNAR and ER beta were coexpressed in 35 (50%), individually in 17 (24.2%), and negative in 18 (25.7%) tumors. PELP1 / MNAR staining was predominantly cytoplasmic whereas ER beta staining was nuclear and occasionally cytoplasmic in tumor cells. Our results indicate that PELP1 / MNAR and ER beta are coexpressed in most SDCs and may play a role in the pathobiology of these tumors.

摘要

涎腺导管癌(SDC)是一种高级别肿瘤,在形态上与乳腺导管癌极为相似。新型雌激素受体(ER)相互作用蛋白以及富含脯氨酸、谷氨酸和亮氨酸的蛋白1(PELP1),也被称为ER非基因组活性调节剂(MNAR),已被证明可通过非基因组和基因组机制激活乳腺癌中的类固醇激素受体。该基因在SDC中的表达及其与ER状态的关系尚不清楚。我们使用蛋白质免疫印迹法和免疫组织化学方法,研究了PELP1/MNAR以及ERα和ERβ蛋白在SDC中的差异表达。对7对正常和肿瘤标本进行的蛋白质免疫印迹分析显示,在3例SDC中PELP1/MNAR表达增加,在4例SDC中ERβ表达增加。在任何正常或SDC标本中均未检测到ERα的表达。对70例SDC进行的免疫组织化学染色显示,51例(73%)肿瘤中PELP1/MNAR呈强表达,52例(74%)肿瘤中ERβ呈强表达。PELP1/MNAR和ERβ在35例(50%)肿瘤中共同表达,在17例(24.2%)肿瘤中单独表达,在18例(25.7%)肿瘤中呈阴性表达。PELP1/MNAR染色主要位于细胞质,而ERβ染色在肿瘤细胞中主要位于细胞核,偶尔位于细胞质。我们的结果表明,PELP1/MNAR和ERβ在大多数SDC中共同表达,可能在这些肿瘤的病理生物学中发挥作用。

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