Expression of periostin in human breast cancer
Expression of periostin in human breast cancer
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DOI：
10.1136/jcp.2007.052506
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Di Loreto, C.
中科院分区：
文献类型：
--
作者：
Puglisi, F.;Puppin, C.;Di Loreto, C.
背景：骨膜素是一种分泌型粘附蛋白，通常在间充质衍生细胞中表达。上皮性肿瘤中骨膜素基因的异常表达似乎在血管生成和转移中发挥作用。目的：研究一系列连续乳腺癌中的骨膜素表达，并将其与已确定的生物学和预后因素相关联。方法：使用特定的抗骨膜素抗体，通过免疫组织化学对连续系列的 206 例乳腺癌进行研究。分析雌激素和孕激素受体、Ki-67 (MIB-1)、HER-2/neu、VEGF-A、VEGFR-1 和 VEGFR-2 的免疫组织化学表达。还通过免疫组织化学、蛋白质印迹和定量 RT-PCR 研究了 MCF-7 和 MDA-468 细胞系中的 Periostin 表达。通过绿色荧光蛋白（GFP）方法研究了MCF-7细胞中periostin的定位。结果：Periostin在癌细胞中高表达，但在正常乳腺组织中不表达。表达模式主要是细胞质。然而，在 12% 的情况下观察到核反应。核骨膜素与肿瘤大小以及雌激素受体、孕激素受体、VEGF-A、VEGFR-1 和 VEGFR-2 的表达显着相关。在 MCF-7 和 MDA-468 细胞系中也观察到骨膜蛋白的核定位。在MCF-7细胞中，通过表达GFP-骨膜素嵌合蛋白的载体转染也显示了骨膜素的核定位。结论：结果表明乳腺癌细胞中骨膜素的异常基因表达与该蛋白的异常核定位有关。乳腺癌中骨膜素的核定位可能会产生显着的生物学效应。
Background: Periostin is a secreted adhesion protein, normally expressed in mesenchime-derived cells. Aberrant expression of the periostin gene in epithelial tumours seems to play a role in angiogenesis and metastases.Aims: To investigate periostin expression in a consecutive series of breast carcinomas and correlate it with established biological and prognostic factors.Methods: A consecutive series of 206 breast carcinomas was investigated by immunohistochemistry with a specific antiperiostin antibody. Immunohistochemical expression of oestrogen and progesterone receptors, Ki-67 (MIB-1), HER-2/neu, VEGF-A, VEGFR-1 and VEGFR-2 was analysed. Periostin expression was also investigated in MCF-7 and MDA-468 cell lines by immunohistochemistry, western blot and quantitative RT-PCR. Localisation of periostin was investigated in MCF-7 cells by the green fluorescent protein (GFP) approach.Results: Periostin was highly expressed in carcinoma cells, but not in normal breast tissues. The pattern of expression was mainly cytoplasmic. However, in 12% of cases a nuclear reactivity was observed. Nuclear periostin significantly correlated with tumour size, and with expression of oestrogen receptor, progesterone receptor, VEGF-A, VEGFR-1 and VEGFR-2. A nuclear localisation of periostin was also observed in MCF-7 and MDA-468 cell lines. In MCF-7 cells the nuclear localisation of periostin was also shown by transfection of a vector expressing a GFP-periostin chimeric protein.Conclusions: Results indicate that the aberrant gene expression of periostin in breast cancer cells is associated with an abnormal nuclear localisation of the protein. The nuclear localisation of periostin in breast cancer may induce significant biological effects.