Role of Sphk1 in the malignant transformation of breast epithelial cells and breast cancer progression

被引:9
|
作者
Zheng, X. D. [1 ,2 ]
Zhang, Y. [1 ]
Qi, X. W. [1 ]
Wang, M. H. [1 ]
Sun, P. [1 ]
Zhang, Y. [1 ]
Jiang, J. [1 ]
机构
[1] Third Mil Med Univ, Southwest Hosp, Breast Dis Ctr, Chongqing 400038, Peoples R China
[2] Chongqing Canc Inst, Breast Dis Ctr, Chongqing 400030, Peoples R China
基金
中国国家自然科学基金;
关键词
Breast cancer; e-cadherin; malignant transformation; metastasis Sphingosine kinase 1;
D O I
10.4103/0019-509X.175343
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: The ojective of the following study is to investigate the role of sphingosine kinase 1 (Sphk1) in the malignant transformation of breast epithelial cells and breast cancer progression and its mechanism. MATERIALS AND METHODS: Immunohistochemistry was performed to detect Sphk1 and E-cadherin (E-cad) in resected breast samples. Sphk1 was transfected in normal human breast epithelial cell line (MCF-10A) by Lentivirus and silenced in breast cancer cell line (MCF-7) using small interfering ribonucleic acid. The effect of tumor necrosis factor alpha (TNF-alpha) and/or N, N-dimethylsphingosine (DMS) on the Sphk1 and E-cad expression, MCF-10A cell proliferation and invasion was investigated. Real time-polymerase chain reaction and western-blot was used to detect messenger ribonucleic acid and protein. Cell counting kit-8 and transwell were used to measure cell proliferation and invasion. RESULTS: Sphk1 was positive expression in 114 breast tumors (75.50%) but negative in fibroadenomas. The expression of E-cad and Sphk1 were negatively correlated and E-cad (-)/Sphk1 (+) carriers showed higher ratio of axillary lymph node metastasis than E-cad (+)/Sphk1 (-) carriers. Overexpression of Sphk1 in MCF-10A reduced E-cad expression and improved cell proliferation and invasion, but knockdown of Sphk1 in MCF-7 decreased cell proliferation and invasion. TNF-alpha increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E-cad expression, which could be blocked by DMS. TNF-alpha promoted MCF-10A cell proliferation and invasion. CONCLUSION: Sphk1 plays an important role in the malignant transformation of breast epithelial cells and modulates breast cancer metastasis through the regulation of E-cad expression. TNF-alpha can up-regulate Sphk1 expression and reduce E-cad expression through Sphk1, which can be blocked by DMS. TNF-alpha/Sphk1/E-cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis.
引用
收藏
页码:524 / U408
页数:6
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