title: Testicular orphan nuclear receptor 4-associated protein 16 promotes             non-small cell lung carcinoma by activating estrogen receptor β and blocking testicular             orphan nuclear receptor 2.
abstract: The possible involvement of estrogen receptors (ERs) and testicular orphan             nuclear receptors (TRs) in human non-small cell lung carcinoma (NSCLC) has been             suggested, but their precise roles and their relationship remain largely unknown.             This study aimed to investigate whether TR4-associated protein 16 (TRA16) regulates             the ERβ and TR2 pathways and could be a potential target in NSCLC. We used tissue             microarrays including NSCLC tissues (n=154) and negative controls (n=14) to examine             the expression of TRA16 and ERβ, and in vitro reporter gene assays, the mammalian             two-hybrid method and immunoprecipitation in Cos-1 cells to investigate the relationships             among TRA16, ERβ and TR2. We found that TRA16 was highly expressed in approximately             90% of the NSCLC tissues examined. TRA16 overexpression was significantly associated             with TNM stage, tumor size, lymph node metastasis, tumor thrombus in vein, tumor             differentiation and prognosis of NSCLC patients, in which TRA16 was shown to be             an independent prognostic factor. Introduction of TRA16 into Cos-1 cells enhanced             cell proliferation. Co-expression of TRA16 and ERβ in Cos-1 cells using different             reporter gene systems and mammalian two-hybrid approaches revealed that TRA16             enhanced ERβ-mediated transcriptional activity. By adopting similar approaches,             and immunoprecipitation and immunocytofluorescence assays, we found that TRA16             also interacted with TR2, and blocked the TR2 inhibitory effect on ERβ. Our findings             demonstrate that TRA16 could be a promising diagnostic and prognostic biomarker             in NSCLC, and promotes cancer cell growth through activation of the ERβ pathway             by interacting with ERβ and TR2.
authors.affiliation: Department of Thoracic Surgery Ⅱ, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zheng
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Sainan
authors.initials: S
authors.lastname: Zhu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Bingtian
authors.initials: B
authors.lastname: Zhao
authors.forename: Shaolei
authors.initials: S
authors.lastname: Li
authors.forename: Hongchao
authors.initials: H
authors.lastname: Xiong
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Sonya Wei
authors.initials: SW
authors.lastname: Song
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D019556:COS Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D047629:Estrogen Receptor beta; C472782:NR2C2AP protein, human; D009687:Nuclear Proteins; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2; D034741:RNA, Small Interfering; D012097:Repressor Proteins