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LZTS2 inhibits proliferation, migration and EMT of breast cancer cells by modulating PI3K/AKT signaling pathway
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Abstract:
[Abstract] Objective: To evaluate the expression of leucine zipper tumor suppressor 2 (LZTS2) in human breast cancer tissues and cell lines, and to investigate the effects and mechanisms of LZTS2 over-expression on proliferation, invasion and epithelial-mesenchymal transition (EMT) of breast cancer cells. Methods: Fifty pairs of cancerous tissues and para-cancerous tissues resected from breast cancer patients in Department of Breast Surgery of Kaifeng Central Hospital from January, 2016 to December, 2016, as well as breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468) and normal mammary epithelial HBL-100 cells were collected for this study;and Real-time quantitative PCR (qPCR) and Western blotting were used to determine the mRNA and protein expressions of LZTS2 in collected tissues and cell lines. MCF-7 cells were transfected with pcDNA-LZTS2 or pcDNA3.1 (negative control) using lipofectamineTM 2000, and the protein expression of LZTS2 at 49-72 h after transfection was measured by Western blotting; Then, the effects of LZTS2 over-expression on proliferation, migration and invasion of MCF-7 cells were detected by MTT assay and Transwell assay, respectively;Furthermore, Western blotting was performed to detect the expressions of EMT associated proteins (Cyclin D1, Vimentin, Ncadherin,E-cadherin) and PI3K/AKT signaling pathways-related molecules. Results: The mRNA and protein expressions of LZTS2 were down-regulated in breast cancerous tissues and cell lines (MCF-7, MDA-MB-468 and MDA-MB-231) as compared with paired para-cancerous tissues or normal mammary epithelial HBL-100 cells (P<0.05 or P<0.01). Compared with and blank control or pcDNA3.1 group, the protein expression of LZTS2 in MCF-7 cells of pcDNA-LZTS2 group significantly increased (P<0.01), while the proliferation,migration and invasion of MCF-7 cells significantly reduced (P<0.05 or P<0.01). In addition, forced expression of LZTS2 significantly down-regulated the protein expressions of Cyclin D1, Vimentin and N-cadherin (P<0.05 or P<0.01) but up-regulated the expression of E-cadherin in MCF-7 cells (P<0.01), indicating LZTS2 over-expression suppressed PI3K / AKT signaling pathway through inhibiting the expression p-PI3K and p-AKT. Conclusion: The findings collectively demonstrated that the expression of LZTS2 was decreased in breast cancer, and over-expression of LZTS2 efficiently inhibited the proliferation, migration and invasion of breast cancer cells, which might be related with the suppression of PI3K/AKT signaling pathway involved in EMT.
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