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ERAP75 functions as a coactivator to enhance estrogen receptor α transactivation in prostate stromal cells
Author(s) -
Chen Ming,
Ni Jing,
Zhang Yong,
Muyan Mesut,
Yeh Shuyuan
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20774
Subject(s) - transactivation , stromal cell , coactivator , prostate cancer , cancer research , estrogen receptor , biology , microbiology and biotechnology , gene knockdown , transcription factor , cell culture , gene , cancer , genetics , breast cancer
BACKGROUND Estrogen receptor α (ERα) has been reported to be expressed and function in the prostate stromal cells, and numerous evidences indicated that the stromal ERα signal pathway plays critical roles in prostate development and cancer. ERα requires distinct coregulators for efficient transcriptional regulation. The goal of this study is to examine physical and functional interaction between ERα and ERAP75 in the context of prostate stromal cells. METHOD Yeast two‐hybrid assays were used to screen novel ERα interaction proteins. The interaction between ERα and ERAP75 was confirmed by mammalian two‐hybrid, GST pull‐down, and co‐immunoprecipitation methods. The interaction motif was examined by site‐directed mutagenesis. The effect of ERAP75 on ERα transactivation and the expression of ERα target genes were determined by luciferase assay and real‐time PCR, respectively. RESULT ERα can interact with the C terminus of ERAP75 via its ligand binding domain both in vivo and in vitro. The conserved LXXLL motif within the C terminus of ERAP75 is required for the interaction between ERα and ERAP75. ERAP75 can enhance ERα transactivation in a dose‐dependent manner and up‐regulate the expression of the endogenous ERα target gene, stromal‐derived factor‐1 (SDF‐1), in the prostate stromal cells. CONCLUSION ERAP75 functions as a novel coactivator that can modulate ERα function in the prostate stromal cells. The understanding of the mechanism of ERα transactivation in prostate stromal cells could possibly help in the development of new strategies to control or treat prostate cancer by targeting its transactivation protein complex. Prostate 68:1273–1282, 2008. © 2008 Wiley‐Liss, Inc.