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Gankyrin 在乳腺癌中经常过表达,并与 ErbB2 表达相关。

Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression.

机构信息

Department of Biochemistry and Molecular Biology, Brain Korea 21 Division of Cell Transformation and Restoration, Ajou University, School of Medicine, Suwon 443-721, Republic of Korea.

出版信息

Exp Mol Pathol. 2013 Apr;94(2):360-5. doi: 10.1016/j.yexmp.2012.12.002. Epub 2012 Dec 28.

Abstract

Gankyrin is a subunit of the 26S proteasome, and has been known to degrade p53 and retinoblastoma protein and promote the tumorigenicity and metastasis in some malignancies. However, the role of gankyrin in breast cancer has not been explored. In this study, we investigated the expression of gankyrin in breast cancer and evaluated its effect on breast cancer. Representative cancer tissues including normal breasts from 60 patients with breast cancer were stained immunohistochemically for gankyrin, estrogen receptor, progesterone receptor, and ErbB2. We evaluated the relationship between gankyrin expression and clinicopathologic parameters or prognostic markers. We also attempted to clarify the mechanism of gankyrin involved in breast carcinogenesis by using MCF7 breast cancer cells. Gankyrin was weakly expressed in normal breast epithelial cells, however, tumor regions of 37/60 (61.7%) cases showed an overexpression of gankyrin. Gankyrin overexpression was associated with extensive intraductal carcinoma (p=0.014) and ErbB2 positivity (p=0.031) in invasive ductal carcinoma. In MCF7 breast cancer cells, downregulation of gankyrin was associated with a reduction of cell proliferation and tumorigenicity. In conclusion, gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer.

摘要

肝醣激酶蛋白是 26S 蛋白酶体的一个亚单位,已知可降解 p53 和视网膜母细胞瘤蛋白,并促进某些恶性肿瘤的致瘤性和转移。然而,肝醣激酶蛋白在乳腺癌中的作用尚未被探索。在这项研究中,我们研究了肝醣激酶蛋白在乳腺癌中的表达,并评估了其对乳腺癌的影响。对 60 例乳腺癌患者的代表性癌组织(包括正常乳腺)进行肝醣激酶蛋白、雌激素受体、孕激素受体和 ErbB2 的免疫组织化学染色。我们评估了肝醣激酶蛋白表达与临床病理参数或预后标志物之间的关系。我们还试图通过 MCF7 乳腺癌细胞来阐明肝醣激酶蛋白参与乳腺癌发生的机制。正常乳腺上皮细胞中肝醣激酶蛋白表达较弱,但 60 例中的 37 例(61.7%)肿瘤区域呈现肝醣激酶蛋白过表达。肝醣激酶蛋白过表达与乳腺浸润性导管癌的广泛导管内癌(p=0.014)和 ErbB2 阳性(p=0.031)有关。在 MCF7 乳腺癌细胞中,肝醣激酶蛋白下调与细胞增殖和致瘤性降低有关。总之,肝醣激酶蛋白在正常乳腺中被鉴定出来,并在浸润性乳腺癌中过表达。肝醣激酶蛋白的过表达与乳腺癌中的广泛导管内癌和 ErbB2 表达有关。

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