title: Upregulation of RPA2 promotes NF-κB activation in breast cancer by relieving the antagonistic function of menin on NF-κB-regulated transcription.
abstract: RPA2, a subunit of the heterotrimeric replication protein A (RPA) complex, is overexpressed in various cancers. In this study, we showed a significant RPA2 upregulation in breast cancer tissues and cell lines. Ectopic expression of RPA2 in MCF7 and MDA-MB-231 cells promoted cell proliferation, adhesion, migration and invasion, and induced epithelial-mesenchymal transition (EMT) of MCF7 cells. Ablation of RPA2 in MDA-MB-231 cells induced apoptosis and suppressed colony formation, EMT and invasion. Binding assays indicated that menin, the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene product, interacted with RPA2. Ectopic expression of RPA2 inhibited the formation of the menin-NK-κB p65 complex and repressed the inhibitory effect of menin on expression of NF-κB-regulated genes that contribute to tumor progression. Conversely, knockdown of RPA2 promoted formation of the menin-p65 complex and repressed the expression of NF-κB-mediated genes. RPA2 expression was induced via an E2F1-dependent mechanism in MCF7 and MDA-MB-231 cells treated with NF-κB activators, TNF-alpha or lipopolysaccharide (LPS). These results suggested that RPA2-dependent tumorigenicity was mediated via enhancement of NF-κB activity by relieving the antagonistic function of menin on NF-κB-regulated transcription in breast cancer cells.
authors.affiliation: Department of Biotechnology, College of Medicine and Nursing, Hung Kuang University, Taichung 43302, Taiwan.
authors.forename: Chao-Chung
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Emergency, Kuang Tien General Hospital, Taichung 43302, Taiwan.|Department of Nursing, College of Medicine and Nursing, Hung Kuang University, Taichung 43302, Taiwan.
authors.forename: Chi-Wen
authors.initials: CW
authors.lastname: Juan
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.affiliation: Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan 70101, Taiwan and.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan 70101, Taiwan and.
authors.forename: Janq-Chang
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Nutrition, College of Medicine and Nursing, Hung Kuang University, Taichung 43302, Taiwan.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051716:Replication Protein A / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: C105373:MEN1 protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051716:Replication Protein A; C516794:RPA2 protein, human