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

摘要

Background: Radiotherapy is an effective and important therapeutic method for breast cancer, but at the same time it has a radiation-induced bystander effect on normal tissue 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 transduction. However, the response of normal human mammary epithelial cells following low dose radiation (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 (IV1CF10A) and Cav-1 haplo-insufficiency (MCF10A-ST1) cells were irradiated with LDR gamma rays and the effect of this radiation on cell proliferation was determined by cytometric method. Western blot analysis was then used to measure the expression levels of different proteins associated with cell proliferation and DNA repair. Results: LDR enhanced the radiation responsiveness of MCF10A cells in a dose- and time-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 activated Cav-1-mediated cell proliferation and survival pathways, such as the MAPK and AKT pathways. The expression of the various DNA repair related proteins was changed after down-regulating the Cav-1 expression. Conclusion: LDR could increase the radiation responsiveness of human mammary epithelial cells through activating the DNA repair pathways, including both HR and NHEJ pathways, as well as triggering the cell proliferation and survival pathways, both of which required Cav-1.