Molecular Endocrinology, Vol 8, 448-455, Copyright © 1994 by Endocrine Society

ARTICLES

The mouse androgen receptor is suppressed by the 5'-untranslated region of the gene

ME Grossmann, J Lindzey, MV Kumar and DJ Tindall
Department of Urology, Mayo Foundation, Rochester, Minnesota 55905.

The androgen receptor (AR) mediates the biological functions of androgens and is essential for normal growth and differentiation of urogenital organs as well as initiation and maintenance of spermatogenesis. Withdrawal of androgens by castration or other methods has been shown to cause a marked, although often temporary, regression of many prostate cancers. In order to gain a better understanding of the transcriptional regulation of the AR, a series of truncation mutants derived from the 5'-region of the mouse AR (mAR) were inserted into the promoter-less plasmid pBLCAT3 and transiently expressed in the mouse alpha T3-1 and GT1-7 cell lines. The results of these experiments indicate the presence of a negative regulatory element in the 5'- untranslated region of the gene, which is able to reduce chloramphenicol acetyltransferase (CAT) activity by 77-89%. We have named this element the mAR suppressor (mARS). DNase-I protection assays of the 5'-untranslated region disclosed a protected domain. Gel mobility assays using the mARS revealed the presence of three protein- DNA complexes that could specifically bind to this protected domain. Insertion of the mARS into the thymidine kinase promoter containing pBLCAT2 vector resulted in a 2- to 10-fold decrease in CAT activity, but only if the insert was 3' to the start of transcription initiation. Finally, point mutations within the mARS were able to increase transcription of the AR promoter by 2.3-fold. The results of these experiments indicate that the mAR 5'-untranslated region contains a suppressor element.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				X. Ye, S. J. Han, S. Y. Tsai, F. J. DeMayo, J. Xu, M.-J. Tsai, and B. W. O'Malley Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice PNAS, July 5, 2005; 102(27): 9487 - 9492. [Abstract] [Full Text] [PDF]

				X. F. Lu, X. G. Jiang, Y. B. Lu, J. H. Bai, and Z. B. Mao Characterization of a Novel Positive Transcription Regulatory Element That Differentially Regulates the Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Gene in Senescent Cells J. Biol. Chem., June 17, 2005; 280(24): 22606 - 22615. [Abstract] [Full Text] [PDF]

				P. Berardi, M. Meyyappan, and K. T. Riabowol A Novel Transcriptional Inhibitory Element Differentially Regulates the Cyclin D1 Gene in Senescent Cells J. Biol. Chem., February 21, 2003; 278(9): 7510 - 7519. [Abstract] [Full Text] [PDF]

				Long. G. Wang, L. Ossowski, and A. C. Ferrari Overexpressed Androgen Receptor Linked to p21WAF1 Silencing May Be Responsible for Androgen Independence and Resistance to Apoptosis of a Prostate Cancer Cell Line Cancer Res., October 1, 2001; 61(20): 7544 - 7551. [Abstract] [Full Text] [PDF]

				S.-W. Jiang, K. Wu, and N. L. Eberhardt Human Placental TEF-5 Transactivates the Human Chorionic Somatomammotropin Gene Enhancer Mol. Endocrinol., June 1, 1999; 13(6): 879 - 889. [Abstract] [Full Text]

				E. W. Bush, C. S. Taft, G. E. Meixell, and M. B. Perryman Overexpression of Myotonic Dystrophy Kinase in BC(3)H1 Cells Induces the Skeletal Muscle Phenotype J. Biol. Chem., January 5, 1996; 271(1): 548 - 552. [Abstract] [Full Text] [PDF]

				M. E. Grossmann and D. J. Tindall The Androgen Receptor Is Transcriptionally Suppressed by Proteins That Bind Single-stranded DNA J. Biol. Chem., May 5, 1995; 270(18): 10968 - 10975. [Abstract] [Full Text] [PDF]