Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast cancer.
Peroxiredoxin III (Prx III), an antioxidant protein found in mitochondria, plays an essential role in mitochondrial homeostasis. Aberrant expression of Prx III has been implicated in the tumorigenesis of various cancers. In this study, we evaluated the expression of Prx III in breast cancer tissues and elucidated its role in cell proliferation, a hallmark of cancer. Breast tissue microarrays comprising 106 breast cancer sections were stained with Prx III antibody using immunohistochemisty and correlated with proliferating cell nuclear antigen (PCNA) immunostaining. To validate the role of Prx III in cell proliferation, expression of Prx III was analyzed at the mRNA and protein levels by real-time RT-PCR, Western blotting and immunofluorescence in vitro. siRNA mediated silencing of Prx III in MDA-MB-231 breast cancer cells was performed and the effect on the cell cycle was examined. Prx III expression in patient tissue microarray samples was found to be positively associated with PCNA immunostaining, a proliferative marker. Prx III was expressed in both MCF-7 and MDA-MB-231 breast cancer cell lines and transient transfection with siPrx III in MDA-MB-231 cells induced inhibition of cell proliferation and cell cycle arrest. The data suggests that Prx III has a significant role in cell cycle regulation and could be a potential proliferation marker in breast cancer.
Chua
Pei-Jou
PJ
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, and Department of Pathology, Singapore General Hospital, MD10, S 117 597, Singapore.
Lee
Eng-Hong
EH
Yu
Yingnan
Y
Yip
George Wai-Cheong
GW
Tan
Puay-Hoon
PH
Bay
Boon-Huat
BH
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D061105:Peroxiredoxin III; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014162:Transfection
D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins