COP1, the negative regulator of ETV1, influences prognosis in triple-negative breast cancer

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• 作者：Mao Ouyang ; Hua Wang ; Jieyi Ma ; Weiming Lü ; Jie Li ; Chen Yao ; Guangqi Chang…
• 关键词：ETV1 ; COP1 ; Triple ; negative breast cancer ; Overall survival ; Prognosis
• 刊名：BMC Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：2,110 KB
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• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

Background ETS variant 1 (ETV1) and E3 ubiquitin ligase constitutive photomorphogenetic 1 (COP1) have been proposed to be a pair of oncogene and tumor suppressor. However, the co-existing status of ETV1 and COP1 in triple-negative breast cancer (TNBC) and their predictive role in determining the patient’s outcome are uncertain. Methods We examined the abundance of COP1 and ETV1 proteins and their clinicopathologic significance in archival TNBC tissues from 105 patients by tissue microarray. The potential function link between COP1 and ETV1 was observed in MDA-MB-231 cells by cell proliferation, invasion and migration assays. Results ETV1 expression was higher in TNBC tissues compared to normal tissues, while COP1 was lower. ETV1 expression was negatively associated with COP1 abundance in TNBCs. Overexpression of COP1 led to significant reduction of ETV1 in MDA-MB-231 cells, and suppressed the cells migration and invasion. Rescue of ETV1 expression in the presence of COP1 notably regained the cells behaviors. ETV1-positive group was associated with a markedly poor overall survival. Meanwhile, we had observed favourable prognosis in COP1-positive cases for the first time. Multivariate analysis showed that COP1 together with ETV1 were independent risk factors in the prognosis of TNBC patients. Conclusions COP1 might be a tumor suppressor by negative regulating ETV1 in patients with TNBCs. COP1 and ETV1 are a pair of independent predictors of prognosis for TNBC cases. Thus, targeting them might be a potential strategy for personalized TNBC treatment.