title: MEIS1 functions as a potential AR negative regulator.
abstract: The androgen receptor (AR) plays critical roles in human prostate carcinoma progression and transformation. However, the activation of AR is regulated by co-regulators. MEIS1 protein, the homeodomain transcription factor, exhibited a decreased level in poor-prognosis prostate tumors. In this study, we investigated a potential interaction between MEIS1 and AR. We found that overexpression of MEIS1 inhibited the AR transcriptional activity and reduced the expression of AR target gene. A potential protein-protein interaction between AR and MEIS1 was identified by the immunoprecipitation and GST pull-down assays. Furthermore, MEIS1 modulated AR cytoplasm/nucleus translocation and the recruitment to androgen response element in prostate specific antigen (PSA) gene promoter sequences. In addition, MEIS1 promoted the recruitment of NCoR and SMRT in the presence of R1881. Finally, MEIS1 inhibited the proliferation and anchor-independent growth of LNCaP cells. Taken together, our data suggests that MEIS1 functions as a novel AR co-repressor.
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing 100853, PR China; Department of Urology, Civil Aviation General Hospital/Civil Aviation Medical College of Peking University, Beijing 100123, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Gastroenterology, Nan Lou Division, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Command, Shenyang 110016, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.affiliation: Beijing Institute for Neuroscience, Capital Medical University, Beijing 100069, PR China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Scientific Data Sharing Platform for Population and Health, Beijing 100730, PR China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Hang
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Electronic address: cuijn@ucmail.uc.edu.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing 100853, PR China. Electronic address: jpgao@163.com.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Gao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C410798:AR protein, human; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D011944:Receptors, Androgen
keywords: Androgen; Androgen receptor; Gene expression; MEIS1; Physical protein interaction; Prostatic carcinoma; Transcriptional activity