The Endocrinology and Developmental Biology of the Prostate*

Cunha, Gerald R.; Donjacour, Annemarie A.; Cooke, Paul S.; Mee, Sharron; Bigsby, Robert M.; Higgins, Stephen J.; Sugimura, Yoshiki

doi:10.1210/edrv-8-3-338

Cited by 966 publications

(705 citation statements)

References 87 publications

(138 reference statements)

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“…The normal human prostatic ductal morphogenesis, partially regulated by sonic hedgehog (Barnett et al, 2002), occurs in two separate periods, prenatally and pubertally (Cunha et al, 1987;Kellokumpu-Lehtinen et al, 1980;Lowsley, 1912). We identified Ck6a+ cells in the urogenital sinus, in fetal and juvenile prostatic glands, and in the fetal stroma.…”

Section: Discussionmentioning

confidence: 92%

Identification of a stem cell candidate in the normal human prostate gland

Schmelz

Moll

Hesse

et al. 2005

European Journal of Cell Biology

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Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+ cells). The Ck6a+ cells are present within a specialized niche in the basal cell compartment in fetal, juvenile and adult prostate tissue, and within the stem cell-enriched urogenital sinus. In adult normal prostate tissue, the average abundance of Ck6a+ cells was 4.9%. With proliferative stimuli in the prostate organ culture model, in which the epithelial-stromal interaction was maintained, a remarkable increase of Ck 6a expression was noticed to up to 64.9%. The difference in cytokeratin 6a expression between the normal adult prostate and the prostate organ culture model was statistically significant (p<0.0001). Within the prostate organ culture model the increase of cytokeratin 6a-expressing cells significantly correlated with increased proliferation index (r = 0.7616; p = 0.0467) The Ck6a+ cells were capable of differentiation as indicated by their expression of luminal cell markers such as ZO-1 and prostate specific antigen (PSA). Our data indicate that Ck6a+ cells represent a prostatic epithelial stem cell candidate possessing high potential for proliferation and differentiation. Since the development of benign prostatic hyperplasia and prostate carcinogenesis are disorders of proliferation and differentiation, the Ck6a+ cells may represent a major element in the development of these diseases.

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Section: Discussionmentioning

confidence: 92%

Identification of a stem cell candidate in the normal human prostate gland

Schmelz

Moll

Hesse

et al. 2005

European Journal of Cell Biology

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“…Speci®cally, the rodent prostate comprises three lobes, namely dorsolateral, ventral and anterior (also called the coagulating gland) that are positioned circumferentially around the urethra. The human prostate is alobular but can be subdivided into three zones ± central, peripheral and transitional ± and completely envelops the upper part of the urethra (Cunha et al, 1987;Maini et al, 1997). Perhaps because of these species-speci®c di erences in physiology, pathology and morphology of the prostate, there is a camp that argues that the mouse is not an ideal organism for the development of a model for human prostate cancer.…”

Section: Existing Modelsmentioning

confidence: 99%

Mouse models of prostate cancer

Sharma

Schreiber‐Agus

1999

Oncogene

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“…One important target tissue of androgens and AR is the prostate. Like the development of normal prostate, growth and progression of prostate cancer are also dependent on androgens and AR (reviewed by Cunha et al, 1987). Although this has been known for many years, only recent work has clearly demonstrated the importance of AR in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Androgen regulation of soluble guanylyl cyclaseα1 mediates prostate cancer cell proliferation

et al. 2006

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The growth and progression of prostate cancer are dependent on androgens and androgen receptor (AR), which act by modulating gene expression. Utilizing a gene microarray approach, we have identified the a1-subunit gene of soluble guanylyl cyclase (sGC) as a novel androgen-regulated gene. A heterodimeric cytoplasmic protein composed of one a and one b subunit, sGC mediates the widespread cellular effects of nitric oxide (NO). We report here that, in prostate cancer cells, androgens stimulate the expression of sGCa1. A cloned human sGCa1 promoter is activated by androgen in an AR-dependent manner, suggesting that sGCa1 may be a direct AR target gene. Disruption of sGCa1 expression severely compromises the growth of both androgendependent and androgen-independent AR-positive prostate cancer cells. Overexpression of sGCa1 alone is sufficient for stimulating prostate cancer cell proliferation. Interestingly, the major growth effect of sGCa1 is independent of NO and cyclic guanosine monophosphate, a major mediator of the sGC enzyme. These data strongly suggest that sGCa1 acts in prostate cancer via a novel pathway that does not depend on sGCb1. Tissue studies show that sGCa1 expression is significantly elevated in advanced prostate cancer. Thus, sGCa1 may be an important mediator of the procarcinogenic effects of androgens.

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The Endocrinology and Developmental Biology of the Prostate*

Cited by 966 publications

References 87 publications

Identification of a stem cell candidate in the normal human prostate gland

Identification of a stem cell candidate in the normal human prostate gland

Mouse models of prostate cancer

Androgen regulation of soluble guanylyl cyclaseα1 mediates prostate cancer cell proliferation

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