title: Autophagic regulation of cell growth by altered expression of Beclin 1 in triple-negative breast cancer.
abstract: Beclin 1 is a promoter gene for autophagy as well as a key factor for regulating tumor cell growth and death. Allelic deletion of Beclin 1 has been observed in certain triple-negative breat cancer (TNBC) cells, and it might be associated with increased proliferation and invasion in TNBC cells. In this study we investigated the relationship between Beclin 1 expression and prognosis for TNBC patients, as well as the influence on cell growth by Beclin 1 overexpression in different cultural conditions. Beclin 1 expression in TNBC tissues was measured by immunohistochemical staining and correlated with clinicopathologic parameters for TNBC patients. The plasmid of pDS-RED-C1-Beclin 1 was transfected to BT-549 and MDA-MB-231 cells and autophagy, proliferation, apoptosis, cell cycle and Epithelial-mesenchymal transition (EMT) process were measured. Results indicated that high level of Beclin 1 expression was correlated with more lymph nodes and distant metastasis but unrelated to survival rates in 5 years for TNBC patients. In vitro, overexpression of Beclin 1 improved cellular autophagy in both BT-549 and MDA-MB-231 cells, inhibited cell proliferation at normal cultural condition and increased cell survival in starvation, hypoxia or with doxorubicin stimulation. Besides, Beclin 1 overexpression decreased cell apoptosis, induced cells to be in G0/G1 phase and promoted EMT process through Wnt/β-catenin pathway in starvation. Thus, Beclin 1 overexpression plays a double role in BT-549 and MDA-MB-231 cell growth by elevating the capability of autophagy. These findings might be useful for searching a proper method for clinical therapy of TNBC from the aspect of autophagy in future.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Wu
authors.affiliation: Department of Obstetrics & Gynecology, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Yi-Zhe
authors.initials: YZ
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Shao
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Ji
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Ri-Wei
authors.initials: RW
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Xu-Long
authors.initials: XL
authors.lastname: Fan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Lin-Hai
authors.initials: LH
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Southern Medical University, Zhujiang Hospital Guangzhou 510282, People's Republic of China.
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Jiao
keywords: Beclin 1 gene; Triple-negative breast cancer; autophagy