Sex steroids have differential effects on growth and gene expression in primary human prostatic epithelial cell cultures derived from the peripheral versus transition zones.
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, p21(waf1/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.
Kirschenbaum
Alexander
A
Division of Endocrinology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Liu
Xin-Hua
XH
Yao
Shen
S
Narla
Goutham
G
Friedman
Scott L
SL
Martignetti
John A
JA
Levine
Alice C
AC
D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000502:physiology; D020869:Gene Expression Profiling; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010641:Phenotype; D011467:Prostate / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000096:biosynthesis; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D019098:Telomerase