An androgen response element mediates LNCaP cell dependent androgen induction of the hK2 gene

Human glandular kallikrein (hK2) is an androgen regulated protein primarily expressed in the prostate and recently identified as a novel prostate canc er marker. A 5 kb 5' fkanking region of the hK2 gene was isolated and seque nced to characterize the regulatory mechanisms for the expression of hK2 in the androgen responsive prostate cell line, LNCaP. Using gene transfer, ge l shift, and mutagenesis assays we have identified an ARE in the 5' far ups tream promoter region of the hK2 gene that is crucial for its regulation in LNCaP cells. This study further demonstrated that the hK2 upstream ARE pla ys a predominant role in androgenic response. More interestingly, previousl y identified AREs in the prostate specific antigen promoter and the hK2 pro ximal promoter exert little activity in LNCaP cells. This study for the fir st time identifies a unique ARE that alone mediates the function of the and rogen receptor in LNCaP cells in a cell dependent manner. This study also e xamines the activity of this ARE with 1 alpha, 25 dihydroxy-vitamin D3 on t he expression of the hK2 gene in LNCaP cells. (C) 2000 Elsevier Science Ire land Ltd. All rights reserved.