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: Liang Cui, Mingyang Li, Fan Feng, Yutao Yang, Xingyi Hang, Jiajun Cui, Jiangping Gao
• Journal: Experimental cell research (Exp Cell Res) Vol. 328 Issue 1 Pg. 58-68 (Oct 15 2014) ISSN: 1090-2422 [Electronic] United States
• PMID: 25158280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• AR protein, human
• Homeodomain Proteins
• MEIS1 protein, human
• Myeloid Ecotropic Viral Integration Site 1 Protein
• Neoplasm Proteins
• Receptors, Androgen

Topics

• Apoptosis
• Blotting, Western
• Cell Adhesion
• Cell Movement
• Cell Nucleus (metabolism)
• Cell Proliferation
• Chromatin Immunoprecipitation
• Cytoplasm (metabolism)
• Gene Expression Regulation, Neoplastic
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Immunoprecipitation
• Male
• Myeloid Ecotropic Viral Integration Site 1 Protein
• Neoplasm Proteins (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Protein Transport
• Receptors, Androgen (genetics, metabolism)
• Response Elements (genetics)
• Signal Transduction
• Transcription, Genetic
• Tumor Cells, Cultured