Oncotarget

Research Papers:

Upregulation of E2F8 promotes cell proliferation and tumorigenicity in breast cancer by modulating G1/S phase transition

Liping Ye, Ling Guo, Zhenyu He, Xi Wang, Chuyong Lin, Xin Zhang, Shu Wu, Yong Bao, Qi Yang, Libing Song and Huanxin Lin _

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Oncotarget. 2016; 7:23757-23771. https://doi.org/10.18632/oncotarget.8121

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Abstract

Liping Ye1,*, Ling Guo2,*, Zhenyu He3,*, Xi Wang4, Chuyong Lin1, Xin Zhang1, Shu Wu1, Yong Bao3, Qi Yang2, Libing Song1, Huanxin Lin3

1Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China

2Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China

3Department of Radiation Oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China

4Department of Breast Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Huanxin Lin, e-mail: linhx@sysucc.org.cn

Keywords: E2F8, proliferation, tumorigenicity, breast cancer, cell cycle

Received: November 02, 2015     Accepted: February 25, 2016     Published: March 16, 2016

ABSTRACT

E2F transcription factors are involved in cell cycle regulation and synthesis of DNA in mammalian cells, and simultaneously play important roles in the development and progression of cancer when dysregulated. E2F8, a novel identified E2F family member, was found to be associated with the progression of several human cancers; however, the biological role and clinical significance of E2F8 in breast cancer remain to be further elucidated. Herein, we report that E2F8 is robustly elevated in breast cancer cell lines and clinical breast cancer tissue samples, respectively. The high expression level of E2F8 significantly correlates with clinical progression (P = 0.001), poor patient survival (P < 0.001) and a high Ki67 staining index (P = 0.008) in 187 human breast cancer specimens. Furthermore, we find that overexpressing E2F8 promotes, whereas silencing E2F8 suppresses, the proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo. We further demonstrate that E2F8 transcriptionally upregulates CCNE1 and CCNE2 via directly interacting with their respective gene promoter, which accelerates the transition of G1 to S phase of breast cancer cells. Taken together, these findings uncover a novel biologic role and regulatory mechanism of E2F8 responsible for the progression of breast cancer, indicating E2F8 may represent a novel prognostic biomarker and therapeutic target against breast cancer.


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