Effect of MMP-2 gene silencing on radiation-induced DNA damage in human normal dermal fibroblasts and breast cancer cells

Genes and Environment

Gugalavath Shailender¹  Seema Kumari¹  Rama Rao Malla¹  Patnala Kiranmayi² 

[1] Cancer Biology Lab, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM (Deemed to be University);Department of Biotechnology, Institute of Science, GITAM Deemed to be University;

关键词: Ionizing radiation;    Matrix metalloproteinase;    DNA damage;    Breast cancer;    Fibroblasts;   

DOI  :  10.1186/s41021-019-0131-x

来源: DOAJ

【 摘 要 】

Abstract Introduction Diagnostic and therapeutic ionizing radiation (IR) is one of the well known long term risk factors of breast cancer. Extremely lethal consequences of IR causes double-strand breaks, which are mainly responsible for genomic instability, altered gene expression, and cell death. Findings This study evaluated the effect of matrix metalloproteinases-2 (MMP-2) gene silencing using MMP-2 shRNA expression plasmids (pMMP-2) on IR induced cytotoxicity and DNA damage by MTT, dead green, γH2AX and comet assays in human normal dermal fibroblasts (HDFs) and MCF-7 human breast cancer cells. IR has decreased the viability of HDFs and MCF-7 cells with increasing IR (2-10Gy). IR induced DNA damage in both HDFs and MCF-7 cells. However, pMMP-2 transfection has increased the viability of irradiated HDFs (10Gy) and significantly decreased the viability of irradiated MCF-7 cells (10Gy). Further, DNA damage in terms of γH2AX foci decreased with pMMP-2 transfection in irradiated HDFs (10Gy) and increased in irradiated MCF-7 cells (10Gy). In addition, MMP-2 gene silencing using pMMP-2 decreased comet tail length in irradiated HDFs but increased in irradiated MCF-7 cells. Conclusions The results conclude that pMMP-2 has protected HDFs and sensitized the MCF-7 cells from IR induced DNA damage. This differential response might be due to IR induced MMP-2 distinctive ROS generation in HDFs and MCF-7 cells.

【 授权许可】

Unknown