Effects of low dose radiation on the expression of proteins related to DNA repair requiring Caveolin-1 in human mammary epithelial cells

Background: Radiotherapy is an effec ve and important therapeu c method for breast cancer, but at the same me it has a radia on-induced bystander effect on normal ssue around the tumor. Repair of double-strand breaks (DSBs) by normal cells can reduce the extent of damage caused by this effect. Caveolin-1 (Cav-1) is an important regulatory molecule in cell signal transduc on. However, the response of normal human mammary epithelial cells following low dose radia on (LDR)induced DSBs and the role of Cav-1 in the repair of the DSBs are not clear. The present study examined the DNA damage repair mechanism triggered by LDR in human mammary epithelial cells. Materials and Methods: Human mammary epithelial (MCF10A) and Cav1 haplo-insufficiency (MCF10A-ST1) cells were irradiated with LDR gamma rays and the effect of this radia on on cell prolifera on was determined by cytometric method. Western blot analysis was then used to measure the expression levels of different proteins associated with cell prolifera on and DNA repair. Results: LDR enhanced the radia on responsiveness of MCF10A cells in a doseand me-dependent manner. At a dose of 100 cGy, LDR increased the expression levels of several proteins involved in DNA repair pathways, such as ATM, p53, DNA-PKcs and also ac vated Cav-1-mediated cell prolifera on and survival pathways, such as the MAPK and AKT pathways. The expression of the various DNA repair related proteins was changed a5er down-regula ng the Cav-1 expression. Conclusion: LDR could increase the radia on responsiveness of human mammary epithelial cells through ac va ng the DNA repair pathways, including both HR and NHEJ pathways, as well as triggering the cell prolifera on and survival pathways, both of which