Open AccessOverexpression of SMAR1 Enhances Radiosensitivity in Human Breast Cancer Cell Line MCF7 via Activation of p53 Signaling Pathway
Author(s) -
Heng-chao Liu,
Fengwang Ma,
Yong Shen,
Yongquan Hu,
Shaojun Pan
Publication year - 2015
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504015x14424348426035
Subject(s) - radiosensitivity , apoptosis , biology , cancer research , mdm2 , cell cycle , cell cycle checkpoint , cell culture , cancer cell , microbiology and biotechnology , cancer , radiation therapy , biochemistry , medicine , genetics
This study sought to investigate the effect of overexpression of SMAR1 (scaffold/matrix-associated region-binding protein 1) on cell radiosensitivity in breast cancer, as well as elucidate its regulatory mechanism. We constructed a lentiviral expression system to successfully overexpress SMAR1 in human breast cancer cell line MCF7. In addition, overexpression of SMAR1 in MCF7 cells enhanced the radiosensitivity to 89 SrCl 2 . Moreover, overexpression of SMAR1 significantly induced cell apoptosis rate and G 2 /M phase arrest under the irradiation of 89 SrCl 2 . In addition, Western blot analysis showed that overexpression of SMAR1 in MCF cells significantly increased the expression levels of pP53 (ser15), pP53 (ser20), acP53, and p21 and obviously decreased the expression of MDM2 under the irradiation of 89 SrCl 2 . Notably, these expression changes could be neutralized by PFTα, an inhibitor of p53 signaling pathway that could inhibit p53-dependent transactivation of p53-responsive genes. Therefore, overexpression of SMAR1 may increase radiosensitivity to 89 SrCl 2 in breast cancer cell line MCF7 by p53-dependent G 2 /M checkpoint arrest and apoptosis. Enhanced expression of SMAR1 in tumors will help to improve the clinical efficiency of radiation therapy.