c-Jun Can Mediate Androgen Receptor-induced Transactivation

c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

“…In contrast, expression of antisense c-Jun had a negative effect. These transcription results are completely consistent with our earlier data using transient transfection experiments (Bubulya et al, 1996(Bubulya et al, , 2000(Bubulya et al, , 2001Tillman et al, 1998;Wise et al, 1998) and strongly suggest that endogenous levels of c-Jun in LNCaP cells are both required and limiting for androgen-regulated gene expression. Although it is not known how widespread the involvement of c-Jun coactivation on the expression of androgen-regulated genes is, it is important to note that all three androgen target genes analysed in this study appear to be regulated by c-Jun coactivation.…”

“…RT-PCR analysis was used to demonstrate that DHT can induce the expression of PSA and TMPRSS2 mRNA in both C33 and, more weakly, C81 cells (Figure 7d). When AR transactivation was measured using MMTV-CAT (Bubulya et al, 1996), both wild-type c-Jun and c-Jun(Ala63/73) were able to stimulate AR transcriptional activity (Figure 7e), but with a lower capacity than what was observed in androgen-dependent LNCaP cells (see Figure 1). These results demonstrate that c-Jun coactivation of AR can occur in both androgen-dependent and androgenindependent LNCaP cells.…”

“…The reporter plasmids MMTV-CAT, TRE-tk-CAT, and PSA-Luc have been previously described (Bubulya et al, 1996;Shenk et al, 2001). Transfection efficiency was standardized by measuring the b-galactosidase activity, originating from the cotransfected plasmid pCH110.…”

“…A103 cells were transfected using FuGENE 6 (Roche, Basel, Switzerland). Cells were incubated with or without 100 nM DHT for 24 h, after which whole-cell extracts were prepared and then subjected to CAT or luciferase assays as described (Bubulya et al, 1996;Shenk et al, 2001). CAT or luciferase assays were standardized according to the measured b-galactosidase activity as previously described (Bubulya et al, 1996).…”

“…While c-Jun represses the transcriptional activity of the AR-related glucocorticoid receptor (GR) (Schule et al, 1990), as well as other nuclear receptors (reviewed in Pfahl, 1993), it strongly potentiates ARmediated transcription (Shemshedini et al, 1992;Bubulya et al, 1996). Several studies from our lab have characterized this coactivator function of c-Jun on AR (Bubulya et al, 1996(Bubulya et al, , 2000(Bubulya et al, , 2001Tillman et al, 1998;Wise et al, 1998). Perhaps the most intereting finding is that c-Jun's function as coactivator can be separated from that of a transactivator, as a transactivationdeficient mutant, c-Jun(Ala63/73), is still active in coactivation (Wise et al, 1998).…”