TY - JOUR
T1 - Regulation of the 5′-flanking region of the mouse androgen receptor gene by cAMP and androgen
AU - Lindzey, Jonathan
AU - Grossmann, Mike
AU - Vijay Kumar, M.
AU - Tindall, Donald J.
PY - 1993/12
Y1 - 1993/12
N2 - Both androgens and cAMP-mediated hormones are known to regulate expression of the androgen receptor (AR) gene. In order to determine whether these effects occur at the transcriptional level, transfection studies were conducted with a 1.5-kilobase fragment of the 5′-flanking region of the mouse AR gene coupled to a chloramphenicol acetyltransferase (CAT) reporter gene. We demonstrated that the cAMP pathway regulates expression of the mouse AR (mAR) 5′-CAT construct in mouse pituitary (αT3-1), rat pituitary (GC), and quail fibroblast (QT6) cell lines. Deletional analysis indicated that several areas of this clone, including a region containing a putative cAMP response element (CRE), are involved in mediating cAMP regulation of the AR gene. Oligonucleotides containing a putative CRE, linked to the thymidine kinase promoter of pBLCAT2, conferred increased forskolin induction of CAT activity. Furthermore, overexpression of a CRE binding protein up-regulated expression of the mAR 5′-CAT constructs. Bandshift data demonstrated that the putative CRE forms specific, competable complexes with nuclear proteins from αT3-1 and QT6 cells. Additional experiments indicated that AR can modulate both basal and forskolin-induced CAT activity in an androgen-dependent fashion. These data provide evidence that the 5′-flanking region of the mAR gene contains sequences which mediate the effects of both cAMP and androgens.
AB - Both androgens and cAMP-mediated hormones are known to regulate expression of the androgen receptor (AR) gene. In order to determine whether these effects occur at the transcriptional level, transfection studies were conducted with a 1.5-kilobase fragment of the 5′-flanking region of the mouse AR gene coupled to a chloramphenicol acetyltransferase (CAT) reporter gene. We demonstrated that the cAMP pathway regulates expression of the mouse AR (mAR) 5′-CAT construct in mouse pituitary (αT3-1), rat pituitary (GC), and quail fibroblast (QT6) cell lines. Deletional analysis indicated that several areas of this clone, including a region containing a putative cAMP response element (CRE), are involved in mediating cAMP regulation of the AR gene. Oligonucleotides containing a putative CRE, linked to the thymidine kinase promoter of pBLCAT2, conferred increased forskolin induction of CAT activity. Furthermore, overexpression of a CRE binding protein up-regulated expression of the mAR 5′-CAT constructs. Bandshift data demonstrated that the putative CRE forms specific, competable complexes with nuclear proteins from αT3-1 and QT6 cells. Additional experiments indicated that AR can modulate both basal and forskolin-induced CAT activity in an androgen-dependent fashion. These data provide evidence that the 5′-flanking region of the mAR gene contains sequences which mediate the effects of both cAMP and androgens.
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M3 - Article
C2 - 7511785
AN - SCOPUS:0027771918
SN - 0888-8809
VL - 7
SP - 1530
EP - 1540
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 12
ER -