Biological role of NHERF1 protein expression in breast cancer
Biological role of NHERF1 protein expression in breast cancer
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DOI：
10.1111/j.1365-2559.2009.03424.x
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发表时间：
2009-11-01
期刊：
影响因子：
6.4
通讯作者：
Paradiso, Angelo
中科院分区：
文献类型：
--
作者：
Mangia, Anita;Chiriatti, Annalisa;Paradiso, Angelo
NHERF1蛋白表达在乳腺癌中的生物学作用目的：确定Na+/H+交换调节因子（NHERF1）在乳腺癌发生和进展中的作用。方法和结果：在一系列回顾性乳腺癌的正常组织、导管原位癌（DCIS）、浸润性癌（IBC）、同步转移淋巴结和异时远处转移中检测NHERF1表达。对51例IBC、42例DCIS和正常组织进行免疫组化检查，并通过免疫荧光研究NHERF1和HER2/neu之间的共定位。 NHERF1 在乳房的不同区室中表现出不同的定位和表达模式。相对于正常组织，配对样本中细胞质 NHERF1 表达的平均值在 DCIS、IBC、远处转移和转移淋巴结中显着更高。此外，在转移性淋巴结中，NHERF1 完全存在于细胞质中。在 DCIS、IBC 和远处转移中，膜上 NHERF1 与过度表达的 HER2/neu 共定位。结论：乳腺癌发生的特点是随着肿瘤的进展，NHERF1 的细胞质表达增加，表明 NHERF1 在此过程中发挥作用。从顶膜表达到细胞质表达的转变与 NHERF1 的双重作用相一致，即依赖于其亚细胞定位的肿瘤抑制因子或肿瘤促进剂。
Biological role of NHERF1 protein expression in breast cancerAims:To determine the role of Na+/H+ exchanger regulatory factor (NHERF1) in breast cancerogenesis and progression.Methods and results:NHERF1 expression was examined in normal tissue, ductal carcinoma in situ (DCIS), invasive carcinoma (IBC), synchronous metastatic lymph node and metachronous distant metastases of a retrospective series of breast cancers. Fifty-one IBC, 42 DCIS and normal tissues were examined immunohistochemically, and the colocalization between NHERF1 and HER2/neu was studied by immunofluorescence. NHERF1 showed a different localization and pattern of expression in the different compartments of the breast. The mean value of cytoplasmic NHERF1 expression in paired samples was significantly higher in DCIS, IBC, distant metastases and metastatic lymph nodes with respect to normal tissues. Moreover, in metastatic lymph nodes NHERF1 was exclusively cytoplasmic. In the membrane NHERF1 was colocalized with overexpressed HER2/neu in DCIS, IBC and distant metastases.Conclusions:Breast cancerogenesis is characterized by increased cytoplasmic expression of NHERF1 as the tumour progresses, suggesting a role in this process. The switch from apical membranous to cytoplasmic expression is compatible with a dual role for NHERF1 as a tumour suppressor or tumour promoter dependent on its subcellular localization.