The prostate gland is the site of two of the most frequent diseases that afflict elderly men: benign prostatic hyperplasia (BPH) and prostate cancer. The etiology of both diseases is thought to involve changes in prostate stem cells, the cells that are responsible for the growth and maintenance of the prostate gland. BPH and prostate cancer arise in different zones of the prostate. If the differences in stem cell biology between the different zones of the human prostate are elucidated, it may be possible to identify the factors regulating the major differences in susceptibility to prostate disease and design more effective means of controlling BPH and prostate cancer.
The specific aims are to identify the epithelial stem cells in each zone of the human prostate and provide the resources for comparative analysis of gene and protein expression in stem cells of these different zones. The project will use normal human prostate tissue to (1) identify, isolate and characterize the epithelial stem cell population from each zone using flow sorting and lineage analysis, (2) to compare the patterns of differentiation between the zones using multiple immunostaining, and (3) to grow and store at least 3 large scale primary cultures of epithelial and mesenchymal cells derived from each zone for future analysis using DNA microarrays and proteomics. It is proposed that this project will lead to a greater understanding of why these two important diseases of elderly men develop in different parts of the prostate and provide the resources needed to develop new strategies for the prevention, management and therapy of BPH and prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG014960-04
Application #
6262467
Study Section
Special Emphasis Panel (ZRG1-UROL (01))
Program Officer
Bellino, Francis
Project Start
2001-03-01
Project End
2004-01-31
Budget Start
2001-03-01
Budget End
2002-01-31
Support Year
4
Fiscal Year
2001
Total Cost
$100,000
Indirect Cost
Name
University of London Institute of Neurology
Department
Type
DUNS #
City
London
State
Country
United Kingdom
Zip Code
Hastie, Claire; Masters, John R; Moss, Stephen E et al. (2008) Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells. J Biol Chem 283:12595-603
Daly-Burns, Bernadette; Alam, Tahirah N; Mackay, Alan et al. (2007) A conditionally immortalized cell line model for the study of human prostatic epithelial cell differentiation. Differentiation 75:35-48
Laczko, Istvan; Hudson, David L; Freeman, Alex et al. (2005) Comparison of the zones of the human prostate with the seminal vesicle: morphology, immunohistochemistry, and cell kinetics. Prostate 62:260-6
Alam, Tahirah N; O'Hare, Michael J; Laczko, Istvan et al. (2004) Differential expression of CD44 during human prostate epithelial cell differentiation. J Histochem Cytochem 52:1083-90
Hudson, D L; Guy, A T; Fry, P et al. (2001) Epithelial cell differentiation pathways in the human prostate: identification of intermediate phenotypes by keratin expression. J Histochem Cytochem 49:271-8
Hudson, D L; O'Hare, M; Watt, F M et al. (2000) Proliferative heterogeneity in the human prostate: evidence for epithelial stem cells. Lab Invest 80:1243-50