The role of androge in determining differentiation and regulation of androgen receptor expression in the human prostatic epithelium transient amplifying population

Heer, R., Robson, C., Shenton, B. and Leung, H. (2007) The role of androge in determining differentiation and regulation of androgen receptor expression in the human prostatic epithelium transient amplifying population. Journal of Cellular Physiology, 212(3), pp. 572-578. (doi: 10.1002/jcp.21154)

Abstract

Abnormal differentiation in epithelial stem cells or their immediate proliferative progeny, the transiently amplifying population (TAP), may explain malignant pathogenesis in the human prostate. These models are of particular importance as differing sensitivities to androgen among epithelial cell subpopulations during differentiation are recognised and may account for progression to androgen independent prostate cancer. Androgens are crucial in driving terminal differentiation and their indirect effects via growth factors from adjacent androgen responsive stroma are becoming better characterised. However, direct effects of androgen on immature cells in the context of a prostate stem cell model have not been investigated in detail and are studied in this work. In alpha 2 beta I hi stem cell enriched basal cells, androgen analogue R 1881 directly promoted differentiation by the induction of differentiation-specific markers CK 18, androgen receptor (AR), PSA and PAP. Furthermore, treatment with androgen down-regulated alpha 2 beta I integrin expression, which is implicated in the maintenance of the immature basal cell phenotype. The alpha 2 beta 1 hi cells were previously demonstrated to lack AR expression and the direct effects of androgen were confirmed by inhibition using the anti-androgen bicalutamide. AR protein expression in a2p 1 hi cells became detectable when its degradation was repressed by the proteosomal inhibitor MG 132. Stratifying the alpha 2 beta 1 hi cells into stem (CID 133(+)) and transient amplifying population (TAP) (CID 133(-)) subpopulations, AR mRNA expression was found to be restricted to the CID 133- (TAP) cells. The presence of a functional AR in the TAP, an androgen independent subpopulation for survival, may have particular clinical significance in hormone resistant prostate cancer, where both the selection of immature cells and functioning AR regulated pathways are involved.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leung, Professor Hing
• Authors: Heer, R., Robson, C., Shenton, B., and Leung, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Cellular Physiology
• ISSN: 0021-9541