1. ¹Department of Molecular Carcinogenesis, The Bob Champion Prostate Stem Cell Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
2. ²Department of Molecular Carcinogenesis, Cell Transformation Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
3. ³Translational Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
4. ⁴Department of Pathology and Molecular Genetics, University of Liverpool, Duncan Building, Liverpool, UK
5. ⁵Department of Oncology, Charing Cross Hospital, London W6 8RF, UK
6. ⁶Ruprecht-Karls-Universitat, Heidelberg Klinikum, Molekular Onkologie, Im Neuenheimer Feld 365, Heidelberg 69120, Germany
7. ⁷Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
8. ⁸Department of Medical Statistics, Royal Marsden NHS Trust, Sutton, Surrey SM2 5NG, UK
9. ⁹Department of Molecular Carcinogenesis, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK

Correspondence: Dr DL Hudson, E-mail: dh560@york.ac.uk

Received 31 July 2008; Revised 16 October 2008; Accepted 16 October 2008; Published online 11 November 2008.

Abstract

Prostate cancer is the most frequently diagnosed male cancer, and its clinical outcome is difficult to predict. The disease may involve the inappropriate expression of genes that normally control the proliferation of epithelial cells in the basal layer and their differentiation into luminal cells. Our aim was to identify novel basal cell markers and assess their prognostic and functional significance in prostate cancer. RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling. We identified 112 and 267 genes defining basal and luminal populations, respectively. The transcription factor TEAD1 and the ubiquitin ligase c-Cbl were identified as novel basal cell markers. Knockdown of either marker using siRNA in prostate cell lines led to decreased cell growth in PC3 and disrupted acinar formation in a 3D culture system of RWPE1. Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics. These data are consistent with basal features impacting on the development and clinical course of prostate cancers.