P6.15PEROXIREDOXIN 3 AS A MOLECULAR THERAPEUTIC TARGET IN BREAST CANCER

ABSTRACT Background: Peroxiredoxins (PRDXs) are a family of enzymes with anti-oxidative functions. To date, there are six mammalian isoforms, viz., PRDX1–6 (located in the different cellular compartments) which have been identified. Each PRDX has diverse functions, which include regulating cell signaling associated with hydrogen peroxide. PRDX3, known to be found exclusively in the mitochondria, has been reported to be elevated in several types of carcinomas. Our previous study has shown that PRDX3 could affect cell proliferation in breast cancer as small interfering RNA (siRNA)-mediated silencing of the PRDX3 gene, reduced cell proliferation in breast cancer cells in vitro. In this study, we evaluated the role of PRDX3 in enhancing breast tumor growth using in vitro and in vivo models, as well as validation with tissue microarrays (TMAs) from breast cancer patients. Materials and methods: siRNA and short hairpin RNA (shRNA) downregulation of the PRDX3 gene were performed in MDA-MB-231 breast cancer cells. Cell cycle-related genes were analyzed by RT-PCR and proliferation by Alamar Blue Assay. For the in vivo model, siPrxIII and siNegative MDA-MB231 breast cancer cells were injected into the mammary pads of female SCID mice. An immunohistochemical study was carried out in TMAs constructed from samples obtained from 152 breast cancer patients. Results: There was decreased expression of cell cycle genes after siRNA-mediated PRDX3 gene knockdown in the MDA-MB-231 breast cancer cells. Moreover, down-regulating the expression of the PRDX3 gene using shRNA, was also associated with a concomitant reduction in cell proliferation in the breast cancer cells. Mice injected with siPrxIII MDA-MB231 breast cancer cells exhibited a reduced breast tumor burden as compared with that observed in control animals. The TMA study also revealed a significant association of PRDX3 protein expression with larger tumor size (P Conclusion: Our data suggests that PRDX3 promotes breast tumorigenesis and could be a potential therapeutic target in breast cancer. Acknowledgement: This study is funded by the National Medical Research Council Singapore.