Carcinogenesis Advance Access published online on August 25, 2005
Carcinogenesis, doi:10.1093/carcin/bgi219
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1 Department of Urology, Mount Sinai School of Medicine, New York, NY 10029
* To whom correspondence should be addressed. The majority of human prostate cancers arise from the peripheral zone. Prostate epithelial stem cells have been localized to the basal epithelial cell compartment. In addition, basal cells have been shown to maintain luminal epithelial cell differentiation and may mediate signals between the stromal and luminal cell compartments. Therefore, the study of adult prostate basal cells derived from different prostate zones may give insights into the mechanisms underlying normal and abnormal prostate growth. We herein compare the basal and sex steroid-stimulated expression and activity of several genes/proteins that are known to be critical in prostate cancer development in primary cultures of basal cells derived from the transition and peripheral zones of prostatectomy specimens. Our results demonstrate that prostate basal cells derived from the peripheral vs. transition zone are more viable in culture, particularly in response to sex steroid addition. Peripheral zone cells exhibit higher telomerase activity and increased expression levels of androgen receptor, the anti-apoptotic protein bcl-2, and the dominant-negative splice variant of Kruppel-like Factor 6. Peripheral zone cells have lower basal expression levels of estrogen receptor-beta, the pro-apoptotic protein Bax, and cell-cycle inhibitor proteins (p53, p21waf1/Cip1). Finally, we demonstrate divergent responses to sex hormones in the two basal cell populations. The gene expression pattern in the peripheral zone cells may partially explain the predominance of prostate cancer development in this region.
Received May 26, 2005
Revised July 22, 2005
Accepted August 19, 2005
CANCER BIOLOGY
Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral vs. transition zones
2 Division of Endocrinology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
3 Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
4 Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029; Department of Oncological Science, Mount Sinai School of Medicine, New York, NY 10029
5 Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029; Department of Oncological Science, Mount Sinai School of Medicine, New York, NY 10029
Alice C. Levine, E-mail: alice.levine{at}mountsinai.org
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