Funding: This work was supported by the Chief Scientist’s Office (CSO) of the Scottish Government (http://www.cso.scot.nhs.uk/): CWH (CZB-4-477) and IH (ETM/382).Peer reviewedPublisher PD

Hay, Colin W

Hunter, Irene

MacKenzie, Alasdair

McEwan, Iain J

PLoS ONE

English

PubMed

Funding: This work was supported by the Chief Scientist’s Office (CSO) of the Scottish Government (http://www.cso.scot.nhs.uk/): CWH (CZB-4-477) and IH (ETM/382).Peer reviewe

Aberdeen University Research

An Sp1 Modulated Regulatory Region Unique to Higher Primates Regulates Human Androgen Receptor Promoter Activity in Prostate Cancer Cells

Colin W. Hay

Irene Hunter

Alasdair MacKenzie

Iain J. McEwan

Crossref

Androgen receptor (AR) mediated signalling is necessary for normal development of the prostate gland and also drives prostate cancer (PCa) cell growth and survival, with many studies showing a correlation between increased receptor levels and therapy resistance with progression to fatal castrate recurrent PCa (CRPC). Although it has been held for some time that the transcription factor Sp1 is the main stimulator of AR gene transcription, comprehensive knowledge of the regulation of the AR gene remains incomplete. Here we describe and characterise in detail two novel active regulatory elements in the 5'UTR of the human AR gene. Both of these elements contain overlapping binding sites for the positive transcription factor Sp1 and the repressor protein pur-α. Aberrant cell signalling is characteristic of PCa and the transcriptional activity of the AR promoter in PCa cells is dependent upon the relative amounts of the two transcription factors. Together with our corroboration of the dominant role of Sp1, the findings support the rationale of targeting this transcription factor to inhibit tumour progression. This should be of particular therapeutic relevance in CRPC where the levels of the repressor pur-α are reduced

Colin W Hay

Iain J McEwan

Directory of Open Access Journals

An Sp1 Modulated Regulatory Region Unique to Higher Primates Regulates Human Androgen Receptor Promoter Activity in Prostate Cancer Cells.

<div><p>Androgen receptor (AR) mediated signalling is necessary for normal development of the prostate gland and also drives prostate cancer (PCa) cell growth and survival, with many studies showing a correlation between increased receptor levels and therapy resistance with progression to fatal castrate recurrent PCa (CRPC). Although it has been held for some time that the transcription factor Sp1 is the main stimulator of AR gene transcription, comprehensive knowledge of the regulation of the AR gene remains incomplete. Here we describe and characterise in detail two novel active regulatory elements in the 5’UTR of the human AR gene. Both of these elements contain overlapping binding sites for the positive transcription factor Sp1 and the repressor protein pur-α. Aberrant cell signalling is characteristic of PCa and the transcriptional activity of the AR promoter in PCa cells is dependent upon the relative amounts of the two transcription factors. Together with our corroboration of the dominant role of Sp1, the findings support the rationale of targeting this transcription factor to inhibit tumour progression. This should be of particular therapeutic relevance in CRPC where the levels of the repressor pur-α are reduced.</p></div

Colin W. Hay (179733)

Irene Hunter (811073)

Alasdair MacKenzie (811074)

Iain J. McEwan (179736)

The Francis Crick Institute

https://figshare.com/articles/_An_Sp1_Modulated_Regulatory_Region_Unique_to_Higher_Primates_Regulates_Human_Androgen_Receptor_Promoter_Activity_in_Prostate_Cancer_Cells_/1570292

An Sp1 Modulated Regulatory Region Unique to Higher Primates Regulates Human Androgen Receptor Promoter Activity in Prostate Cancer Cells

Abstract

Similar works

Full text

Available Versions

Aberdeen University Research

Crossref

Directory of Open Access Journals

The Francis Crick Institute