title: RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.
abstract: Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qiu-Lin
authors.initials: QL
authors.lastname: Ge
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: San-Hong
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Ai
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Min-Fang
authors.initials: MF
authors.lastname: Tao
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Songjiang District Central Hospital, Shanghai, China.
authors.forename: Shan-Yun
authors.initials: SY
authors.lastname: Wen
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Han-Shao
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhuo-Wei
authors.initials: ZW
authors.lastname: Xue
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Sun
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Hu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yong-Xu
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Ding
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Ren
authors.initials: XR
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yin-Cheng
authors.initials: YC
authors.lastname: Teng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009367:Neoplasm Staging; D010641:Phenotype; D016196:S Phase / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C498143:RELA protein, human; C497593:RELB protein, human; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB