Kc. Ho et al., A COMPLEX RESPONSE ELEMENT IN INTRON-1 OF THE ANDROGEN-REGULATED 20-KDA PROTEIN GENE DISPLAYS CELL TYPE-DEPENDENT ANDROGEN RECEPTOR SPECIFICITY, The Journal of biological chemistry, 268(36), 1993, pp. 27226-27235
The androgen-regulated 20-kDa protein gene consists of four exons that
code for a major secretory protein of rat ventral prostate. Analysis
of its potential cis-acting transcriptional regulatory elements reveal
ed that a large intron 1 region (In-1) had stronger androgen response
element (ARE) activity than did the 5'-flanking DNA. In cotransfected
CV1 cells, In-1 and its most active subfragment In-1c functioned as AR
Es but not glucocorticoid response elements (GRE). Nevertheless severa
l ARE/GRE-like partial palindromic sequences are present in In-1c, and
it bound both androgen receptors and glucocorticoid receptors in mobi
lity shift assays. A cluster of three ARE/GRE-like sequences contained
within a 39-base pair sequence of In-1c had both ARE and GRE activiti
es when analyzed as an isolated oligonucleotide, suggesting that other
elements within In-1c determined its ARE specificity. In addition to
ARE/GRE-like sequences, In-1c contains putative response elements for
the transcription factors AP1, CREB, AP2, OCT-1, C/EBP, and a number o
f inverted and direct repeats. The ARE specificity of In-1c observed i
n CV1 cells was diminished in PC3 and HeLa cells transiently cotransfe
cted with an androgen receptor or glucocorticoid receptor expression v
ector together with an In-1c reporter vector; however, the ARE activit
y of In-1c was greater than its GRE activity in these cell lines. Inte
restingly, a 131-base pair subfragment of In-1c retained ARE specifici
ty in all three cell lines.