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学科主题: 临床医学
题名:
Overexpression of the Insulin Receptor Isoform A Promotes Endometrial Carcinoma Cell Growth
作者: Wang, Chun-Fang; Zhang, Guo; Zhao, Li-Jun; Qi, Wen-Juan; Li, Xiao-Ping; Wang, Jian-Liu; Wei, Li-Hui
刊名: PLOS ONE
发表日期: 2013-08-07
DOI: 10.1371/journal.pone.0069001
卷: 8, 期:8
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: IGF-II ; CANCER ; PATHWAY ; EXPRESSION ; INHIBITORS ; APOPTOSIS
英文摘要:

Epidemiological studies have demonstrated that type 2 diabetes mellitus (T2DM) and hyperinsulinemia are associated closely with endometrial carcinoma risk, although the molecular mechanism remains unclear. Insulin receptor isoformA expression is upregulated in many cancer cells and tissues, which suggests that IR-A-mediated signaling pathways may have important implications for cancer pathogenesis. We measured the expression of insulin receptor isoforms (IR-A and IR-B in the normal endometrium tissues, the endometrial carcinoma tissues and the endometrial carcinoma cell lines. We found that the total insulin receptor (IR) and IR-A expression mRNA levels and the ratio of IR-A to total IR in endometrial carcinoma specimens were significantly higher than them in control endometrial tissue specimens(P<0.05). Further analysis indicated that the tendency was more prominently in patients with T2DM. IR-A mRNA was differentially expressed in four endometrial carcinoma cell lines (Ishikawa, KLE, RL95-2 and HEC-1-A. RL95-2 cells have a low endogenous IR-A expression, and these were used to construct a stable cell line overexpressing IR-A. We found that IR-A overexpression significantly increased cell proliferation, the proportion of cells in S phase, activation of the Akt pathway and tumorigenicity of xenografts in nude mice. In contrast, there was no significant difference in the the percentage of apoptotic cells between cells overexpressing IR-A and control cells. Moreover, levels of phosphorylated ERK1/2 protein were significantly decreased in cells overexpressing IR-A relative to controls. These findings reveal the pivotal role of IR-A in endometrial cancer carcinogenesis, and suggest that the association of elevated IR-A levels with cell proliferation and tumorigenicity may be causally linked to its effect on the proportion of cells in S phase and the activation of the Akt pathway.

语种: 英语
所属项目编号: 200800010095 ; 30973181
项目资助者: Specialized Research Fund for the Doctoral Program of Higher Education ; National Natural Science Foundation of China
WOS记录号: WOS:000323109700012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57706
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: Peking Univ, Dept Obstet & Gynecol, Peking Univ Peoples Hosp, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Chun-Fang,Zhang, Guo,Zhao, Li-Jun,et al. Overexpression of the Insulin Receptor Isoform A Promotes Endometrial Carcinoma Cell Growth[J]. PLOS ONE,2013,8(8).
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