基因敲除
顺铂
上皮-间质转换
蜗牛
癌症研究
卵巢癌
生物
转移
免疫组织化学
浆液性液体
癌症
细胞培养
肿瘤科
内科学
医学
免疫学
化疗
生态学
生物化学
遗传学
作者
Noriko Yamaguchi,Rei Mimoto,Nozomu Yanaihara,Yoshimi Imawari,Shinichi Hirooka,Aikou Okamoto,Kiyotsugu Yoshida
出处
期刊:Tumor Biology
[SAGE]
日期:2015-02-25
卷期号:36 (8): 5913-5923
被引量:32
标识
DOI:10.1007/s13277-015-3264-y
摘要
Epithelial-mesenchymal-transition (EMT) plays essential roles in ovarian cancer invasion, metastasis, and drug resistance. A hallmark of EMT is the loss of E-cadherin, which is regulated by Snail. Recently, it was shown that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls Snail degradation in breast cancer. The aim of this study is to clarify whether DYRK2 regulates EMT through Snail degradation in ovarian serous adenocarcinoma (SA). Expression of DYRK2 and Snail in two pairs of cisplatin-resistant and the original cisplatin-sensitive ovarian cancer cell line were analyzed by immunoblotting and real-time RT-PCR analysis. Morphological change, invasion ability, and chemosensitivity were evaluated by using DYRK2 stable knockdown cell line in 2008 (2008 shDYRK2). Immunohistochemical analyses for DYRK2 and Snail were performed with surgical specimens. The correlations between the expression of these proteins and the clinicopathological parameters, including prognosis, were determined. Moreover, we conducted a hypodermic administration test in nude mice and examined reproductive and cisplatin response activities. DYRK2 protein expression was posttranslationally reduced in cisplatin-resistant SA cell lines. 2008 shDYRK2 showed mesenchymal phenotype and resistant to cisplatin. Immunohistochemistry demonstrated that DYRK2 expression inversely correlated with Snail expression, and reduced expression of DYRK2 was associated with shorter overall survival in SA. DYRK2 may regulate EMT through Snail degradation in ovarian SA and might be a predictive marker for a favorable prognosis in the treatment of this cancer.
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