Reduced expression of ubiquitin ligase FBXW7 mRNA is associated with poor prognosis in breast cancer patients
Reduced expression of ubiquitin ligase FBXW7 mRNA is associated with poor prognosis in breast cancer patients
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DOI：
10.1111/j.1349-7006.2010.01801.x
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发表时间：
2011-02-01
期刊：
影响因子：
5.7
通讯作者：
Iwase, Hirotaka
中科院分区：
文献类型：
--
作者：
Ibusuki, Mutsuko;Yamamoto, Yutaka;Iwase, Hirotaka
FBXW 7是一种细胞周期调控基因，其泛素化阳性细胞周期调节因子如c-Myc和细胞周期蛋白E，允许细胞周期退出。FBXW 7基因的缺陷导致细胞周期重新进入并加速G1-S转换，被认为是癌症发展的原因之一。然而，其对乳腺癌患者的临床重要性仍未确定。这促使我们研究其在乳腺癌患者中的表达水平，以确定其临床意义。检测186例原发性浸润性乳腺癌中FBXW 7 mRNA的表达水平。分析FBXW 7 mRNA的表达与临床病理因素、病理分级及Ki-67、FBXW 7、c-Myc、cyclin E免疫组化表达水平的相关性。在乳腺癌细胞系中进行FBXW 7基因沉默的体外研究。FBXW 7 mRNA在高组织学分级和激素受体阴性肿瘤患者中的表达水平显著较低。FBXW 7 mRNA表达较低的患者乳腺癌特异性生存期的预后比表达较高的患者差。高Ki-67标记指数和阳性cyclin E蛋白表达与FBXW 7 mRNA低表达显著相关。在体外，沉默FBXW 7增强c-Myc和细胞周期蛋白E蛋白的表达，上调细胞增殖和G1-S转换。在乳腺癌中，FBXW 7 mRNA表达降低可能通过增强细胞周期调节蛋白的功能而具有独立的预后潜力。（Cancer Sci 2011; 102：439-445）
FBXW7 is a cell cycle regulatory gene that ubiquitinates positive cell cycle regulators such as c-Myc and cyclin E, allowing for cell cycle exit. Defects in the FBXW7 gene that lead to cell cycle re-entry and expedite the G1-S transition is thought to be one of the causes of cancer development. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to establish its clinical significance. The expression level of FBXW7 mRNA was assessed in 186 cases of primary invasive breast cancer. Correlations between FBXW7 mRNA expression and clinicopathological factors, prognoses and immunohistochemical expression levels of Ki-67, FBXW7, c-Myc and cyclin E were analyzed. In vitro investigation of FBXW7 gene silencing in a breast cancer cell line was conducted. FBXW7 mRNA was expressed at significantly lower levels in patients with high histological grade and hormone receptor-negative tumors. Patients with lower FBXW7 mRNA expression had a poorer prognosis for breast cancer-specific survival than those with higher expression. A high Ki-67 labeling index and positive cyclin E protein expression were significantly correlated with lower FBXW7 mRNA expression. In vitro, silencing FBXW7 enhanced expression of c-Myc and cyclin E proteins and upregulated both cell proliferation and G1-S transition. In breast cancer, reduced FBXW7 mRNA expression may have independent prognostic potential through the enhanced function of cell cycle regulatory proteins. (Cancer Sci 2011; 102: 439-445)