PMID- 28007956 OWN - NLM STAT- MEDLINE DCOM- 20170830 LR - 20180510 IS - 1460-2180 (Electronic) IS - 0143-3334 (Linking) VI - 38 IP - 2 DP - 2017 Feb 1 TI - Upregulation of RPA2 promotes NF-kappaB activation in breast cancer by relieving the antagonistic function of menin on NF-kappaB-regulated transcription. PG - 196-206 LID - 10.1093/carcin/bgw123 [doi] AB - 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-kappaB p65 complex and repressed the inhibitory effect of menin on expression of NF-kappaB-regulated genes that contribute to tumor progression. Conversely, knockdown of RPA2 promoted formation of the menin-p65 complex and repressed the expression of NF-kappaB-mediated genes. RPA2 expression was induced via an E2F1-dependent mechanism in MCF7 and MDA-MB-231 cells treated with NF-kappaB activators, TNF-alpha or lipopolysaccharide (LPS). These results suggested that RPA2-dependent tumorigenicity was mediated via enhancement of NF-kappaB activity by relieving the antagonistic function of menin on NF-kappaB-regulated transcription in breast cancer cells. CI - (c) The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Chen, Chao-Chung AU - Chen CC AD - Department of Biotechnology, College of Medicine and Nursing, Hung Kuang University, Taichung 43302, Taiwan. FAU - Juan, Chi-Wen AU - Juan CW AD - Department of Emergency, Kuang Tien General Hospital, Taichung 43302, Taiwan. AD - Department of Nursing, College of Medicine and Nursing, Hung Kuang University, Taichung 43302, Taiwan. FAU - Chen, Kuan-Yu AU - Chen KY AD - Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chang, Yi-Chien AU - Chang YC AD - Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan 70101, Taiwan and. FAU - Lee, Janq-Chang AU - Lee JC AD - Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan 70101, Taiwan and. FAU - Chang, Ming-Chung AU - Chang MC AD - Department of Nutrition, College of Medicine and Nursing, Hung Kuang University, Taichung 43302, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (MEN1 protein, human) RN - 0 (NF-kappa B) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Replication Protein A) RN - EC 2.7.7.7 (RPA2 protein, human) SB - IM MH - Apoptosis/genetics MH - Breast Neoplasms/*genetics/pathology MH - Carcinogenesis/genetics MH - Cell Adhesion/genetics MH - Cell Movement/genetics MH - Cell Proliferation/*genetics MH - Epithelial-Mesenchymal Transition/genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - MCF-7 Cells MH - NF-kappa B/genetics MH - Neoplasm Invasiveness/genetics/pathology MH - Proto-Oncogene Proteins/*genetics/metabolism MH - Replication Protein A/*biosynthesis/genetics MH - Signal Transduction/genetics EDAT- 2016/12/23 06:00 MHDA- 2017/08/31 06:00 CRDT- 2016/12/24 06:00 PHST- 2016/04/20 00:00 [received] PHST- 2016/11/16 00:00 [accepted] PHST- 2016/12/23 06:00 [pubmed] PHST- 2017/08/31 06:00 [medline] PHST- 2016/12/24 06:00 [entrez] AID - bgw123 [pii] AID - 10.1093/carcin/bgw123 [doi] PST - ppublish SO - Carcinogenesis. 2017 Feb 1;38(2):196-206. doi: 10.1093/carcin/bgw123.