Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression
Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression
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DOI：
10.1016/j.yexmp.2012.12.002
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Park, Tae Jun
中科院分区：
文献类型：
--
作者：
Kim, Yeong Hwa;Kim, Jang-Hee;Park, Tae Jun
Gankyrin是26 S蛋白酶体的一个亚基，已知其可降解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，Gankyrin在乳腺癌中的作用尚未被探索。在这项研究中，我们研究了Gankyrin在乳腺癌中的表达，并评估其对乳腺癌的影响。对60例乳腺癌患者的代表性癌组织（包括正常乳腺）进行Gankyrin、雌激素受体、孕激素受体和ErbB 2的化学染色。我们评估了Gankyrin表达与临床病理参数或预后标志物之间的关系。我们还试图通过使用MCF 7乳腺癌细胞来阐明Gankyrin参与乳腺癌发生的机制。Gankyrin在正常乳腺上皮细胞中弱表达，然而，37/60例（61.7%）病例的肿瘤区域显示Gankyrin过表达。Gankyrin过度表达与广泛的导管内癌（p = 0.014）和浸润性导管癌中ErbB 2阳性（p = 0.031）相关。在MCF 7乳腺癌细胞中，Gankyrin的下调与细胞增殖和致瘤性的降低相关。总之，Gankyrin在正常乳腺中被鉴定，在浸润性乳腺癌中过表达。Gankyrin的过度表达与乳腺癌中广泛的导管内癌和ErbB 2的表达有关。(C)2012 Elsevier Inc. All rights reserved.
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. (C) 2012 Elsevier Inc. All rights reserved.