LB-204

Androgen regulates the transcription of target genes through androgen receptor (AR) and plays an important role in prostate cancer cell proliferation and apoptosis. Among the target genes, genes involved in fatty acid synthesis, are reported to be up-regulated by activation of sterol regulatory element-binding protein-1 (SREBP1) rather than a direct action of androgen. In present study, we showed that the removal of multiple Sp1 bindings abolished androgen-mediated transcriptional activation of ATP-citrate lyase promoter in LNCaP cells, whereas these mutations did not affect SREBP1-mediated activation in non-androgen dependent cells, such as PC3 cells. Androgen did not activate the minimal promoter containing multiple copies of SREs but significantly enhanced the transcription by the addition of multiple copies of Sp1-binding sites. Taken together, the recruitments of the coactivators by multiple Sp1-bindings in ATP-citrate lyase promoter could activate the transcription in concert with preoccupied SREBP-1. The multiple Sp1- and SREBP-binding sites are commonly found in other lipogenic enzyme promoters, such as fatty acid synthase and acetyl-CoA carboxylase, which might enable these genes to be specifically activated by androgen in prostate cancer cells.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA