Androgen Regulation of the Human Ornithine Decarboxylase Promoter in Prostate Cancer Cells

We studied the response of the human ornithine de- carboxylase (ODC) promoter to androgen in human prostate cancer cell lines. In the well-differentiated, androgen-sensitive human pros- tate cancer line LNCaP, a genomic ODC promoter fragment that includes putative androgen response elements was suppressed by androgen. In contrast, the androgen-regulated probasin promoter was induced by androgens. The ODC promoter was also induced by cotransfected androgen recepter in the poorly differentiated, an- drogen-insensitive human prostate cancer cell line PPC-1. We ex- amined the effects of cotransfected mutant androgen receptors con- taining the LNCaP mutation or DNA-binding mutations. All cotrans- fected androgen receptors switched the ODC androgen response from suppression to induction in LNCaP cells. Gel-shift and DNA footprint assays demonstrated androgen receptor binding to an ODC sequence that does not contain a consensus androgen response element. Deletion of the sequence abolished androgen suppression of the ODC promoter. We propose a model of pleiotropic gene reg- ulation by androgen that requires a regulatory balance between an- drogen receptor and a transcription factor binding to the nonconsen- sus androgen response element.