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PMID: 8643607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 11 ·1996-05-28 ·Pages 5517-21

Yeh S, Chang C

Abstract

The androgen receptor (AR) is a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. Mutations or abnormal expression of AR in prostate cancer can play a key role in the process that changes prostate cancer from androgen-dependent to an androgen-independent stage. Using a yeast two-hybrid system, we were able to isolate a ligand-dependent AR-associated protein (ARA70), which functions as an activator to enhance AR transcriptional activity 10-fold in the presence of 10(-10) M dihydrotestosterone or 10(-9) M testosterone, but not 10(-6) M hydroxyflutamide in human prostate cancer DU145 cells. Our data further indicated that ARA70 Will only slightly induce the transcriptional activity of other steroid receptors such as estrogen receptor, glucocorticoid receptor, and progesterone receptor in DU145 cells. Together, these data suggest that AR may need a specific coactivator(s) such as ARA70 for optimal androgen activity.

MeSH Terms

Amino Acid Sequence Base Sequence Blotting, Northern Cell Line Chloramphenicol O-Acetyltransferase/biosynthesis Cloning, Molecular DNA-Binding Proteins/metabolism Dihydrotestosterone/pharmacology Flutamide/analogs & derivatives,pharmacology Humans Male Molecular Sequence Data Nuclear Receptor Coactivators Oncogene Proteins Prostate/metabolism Prostatic Neoplasms RNA, Messenger/biosynthesis Receptors, Androgen/metabolism Receptors, Steroid/biosynthesis,metabolism Recombinant Proteins/biosynthesis,metabolism Testosterone/pharmacology Trans-Activators/biosynthesis,metabolism Transcription Factors Transcription, Genetic/drug effects Transfection Tumor Cells, Cultured

Chemicals

DNA-Binding Proteins NCOA4 protein, human Nuclear Receptor Coactivators Oncogene Proteins RNA, Messenger Receptors, Androgen Receptors, Steroid Recombinant Proteins Trans-Activators Transcription Factors Dihydrotestosterone hydroxyflutamide Testosterone Flutamide Chloramphenicol O-Acetyltransferase

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Yeh S

Department of Medicine and University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison 53792, USA.

Chang C

References (18)

18 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.93.11.5517

Published

1996-05-28

Pages

5517-21

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC39278

Subset

Databases

GENBANK

L49399

External Links

PubMed source DOI: 10.1073/pnas.93.11.5517 PMC Full Text View journal details

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Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells.

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