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 ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 524-529

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


1 Breast Disease Center, Southwest Hospital, Third Military Medical University; Breast Disease Center, Chongqing Cancer Institute, Chongqing 400030, China
2 Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

Correspondence Address:
J Jiang
Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038
China
Y Zhang
Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing
China
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Source of Support: National Natural Science Foundation of China (No. 81072156), Science and Technology Application Development Project of Chongqing (No. cstc2013jcsf0143) and Project of Chongqing city health bureau (No. 2012.2.505)., Conflict of Interest: None


DOI: 10.4103/0019-509X.175343

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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-α) 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-α increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E-cad expression, which could be blocked by DMS. TNF-α 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-α can up-regulate Sphk1 expression and reduce E-cad expression through Sphk1, which can be blocked by DMS. TNF-α/Sphk1/E-cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis.






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