Journal Article

Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral versus transition zones

Alexander Kirschenbaum, Xin-Hua Liu, Shen Yao, Goutham Narla, Scott L. Friedman, John A. Martignetti and Alice C. Levine

in Carcinogenesis

Volume 27, issue 2, pages 216-224
Published in print February 2006 | ISSN: 0143-3334
Published online August 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi219
Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral versus transition zones

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The majority of human prostate cancers arise from the peripheral zone (PZ). 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 zone (TZ) and PZ of prostatectomy specimens. Our results demonstrate that prostate basal cells derived from the PZ versus TZ are more viable in culture, particularly in response to sex steroid addition. PZ 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. PZ 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 PZ cells may partially explain the predominance of prostate cancer development in this region.

Keywords: AR, androgen receptor; BPH, benign prostatic hyperplasia; CK, cytokerotin; E2, 17β-estadiol; ER, estrogen receptor; DHT, dihydrotestosterone; HGPIN, high grade prostatic intraepithelial neoplasia; hTERT, human telomerase reverse transcriptase subunit; KLF6, Kruppel-like zinc finger transcription factor; PSA, prostate specific antigen; PSMA, prostate specific membrane antigen; PZ, peripheral zone; SNP, single nucleotide polymorphism; TZ, transition zone

Journal Article.  6625 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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