GAAAATATGATA-like elements in androgen-associated regulation of the prostatic acid phosphatase gene

Abstract

Purpose of the study was to clarify molecular mechanisms behind tissue-specific and hormone-dependent gene expression using human prostatic acid phosphatase (hPAP) gene as a model. Regulatory region −734/+467 of hPAP gene induces transcription of a reporter gene in the prostate of transgenic mice. It contains five elements, A–E, homologous to GAAAATATGATA sequence, which is connected to prostate-specific and androgen-dependent gene expression. The significance of the C, D and E elements in the transcriptional regulation of hPAP gene was evaluated using reporter gene assays. The deletion of element C from the hPAP promoter constructs mainly decreased their transcriptional activity in the presence of androgen, while increased activity particularly in the absence of androgens was detected after removal of elements D and E. These events took place in transiently transfected prostatic LNCaP cells, but not in non-prostatic COS-1 cells. As a conclusion, the GAAAATATGATA-like elements are involved in the transcriptional regulation of hPAP promoter constructs in prostatic cells. These elements mediate both transcriptional activation and repression depending on the hormonal status of the cells and location of the element in the construct.