Clinical Experimental Oncology Laboratory, National Cancer Institute, Bari, Italy.
Histopathology. 2009 Nov;55(5):600-8. doi: 10.1111/j.1365-2559.2009.03424.x.
To determine the role of Na+/H+ exchanger regulatory factor (NHERF1) in breast cancerogenesis and progression.
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.
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.
确定 Na+/H+ 交换体调节因子 (NHERF1) 在乳腺癌发生和进展中的作用。
我们回顾性研究了一系列乳腺癌患者的正常组织、导管原位癌 (DCIS)、浸润性癌 (IBC)、同步转移性淋巴结和异时性远处转移组织，检测了 NHERF1 的表达情况。我们对 51 例 IBC、42 例 DCIS 和正常组织进行了免疫组织化学检测，并通过免疫荧光研究了 NHERF1 与 HER2/neu 的共定位情况。NHERF1 在乳腺的不同部位表现出不同的定位和表达模式。与正常组织相比，DCIS、IBC、远处转移和转移性淋巴结中细胞质 NHERF1 表达的平均值明显更高。此外，在转移性淋巴结中，NHERF1 仅为细胞质。在膜上，NHERF1 与过度表达的 HER2/neu 在 DCIS、IBC 和远处转移中发生共定位。
乳腺癌的发生伴随着 NHERF1 细胞质表达的增加，随着肿瘤的进展，这表明其在这一过程中发挥作用。从顶端膜到细胞质表达的转变与 NHERF1 的双重作用一致，其作为肿瘤抑制因子或肿瘤促进因子取决于其亚细胞定位。
