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Title: MEIS1 functions as a potential AR negative regulator

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. - Highlights: • A potential interaction was identified between MEIS1 and AR signaling. • Overexpression of MEIS1 reduced the expression of AR target gene. • MEIS1 modulated AR cytoplasm/nucleus translocation. • MEIS1 inhibited the proliferation and anchor-independent growth of LNCaP cells.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [1]
  1. Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing 100853 (China)
  2. (China)
  3. Department of Gastroenterology, Nan Lou Division, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing 100853 (China)
  4. Department of Pharmacy, General Hospital of Shenyang Military Command, Shenyang 110016 (China)
  5. Beijing Institute for Neuroscience, Capital Medical University, Beijing 100069 (China)
  6. National Scientific Data Sharing Platform for Population and Health, Beijing 100730 (China)
  7. Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States)
Publication Date:
OSTI Identifier:
22416942
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 328; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANDROGENS; ANTIGENS; CARCINOMAS; CELL PROLIFERATION; CYTOPLASM; GENES; PROSTATE; RECEPTORS; TRANSCRIPTION FACTORS