Proliferation Of Prostate Epithelium Research Articles

Quantitative Stereological Estimations of Structural Patterns of the Glandular Tree in Benign Hyperplasia of Prostate

Background: Benign prostate hyperplasia (BPH) is the most common benign disease of human prostate. Currently BPH is associated with unregulated proliferation of connective tissue and glandular epithelium within the prostatic transition zone, and it has been described as relevant characteristic of BPH—the increase of the total number of cells, and not only an increase in cell size. To date, there are few studies on the quantitative morphology of glandular tree of BPH compared with normal prostate. The scarce investigations about this particular suggest that the glandular tree branches and expands as the hyperplastic transformation occurs in the prostate. Methods: To verify if this gland expansion and branching was similar to that occurs in the normal prostate, this study deals with the estimation of several stereological parameters as: labeling index for the proliferating cell nuclear antigen to quantify the rate of proliferation of prostate epithelium, average thickness of glandular epithelium, fraction of the volume occupied by the epithelium relative to the total prostate volume, connectivity density of prostate glands, to quantify the branching of prostate glands, and the average volume and the volume-weighted mean glandular volume of prostate acini to assess the mean size of the prostate acini and its variability. Results: All these estimates have been performed in prostate specific antigen immunostained sections from prostates of young men (controls) and in adenomectomy specimens from the adenofibromiomatous variety of BPH. Conclusion: We conclude that the epithelial proliferation is not the only factor intervening in the development of BPH. In addition, a more prolonged survival of epithelial population, together with some degree of hypertrophy of acini expressed by the increase of volume fraction and thickness of acinar epithelium, is relevant in order to the growth and expansion of the BPH glandular tree that shows more abundant and heterogeneous acinar sprouts than in normal prostate.

Altered differentiation and proliferation of prostate epithelium in mice lacking the androgen receptor cofactor p44/WDR77.

Although it has been observed that various cofactors modulate activity of the androgen receptor (AR), the specific relationship between AR cofactors and prostate development and functions has not been well studied. To determine whether AR cofactor p44/WDR77 is important in prostate growth and development, we examined prostate architecture in p44/WDR77-null mice and wild-type (WT) littermates. Prostate glands from p44/WDR77-deficient animals were not only smaller than those from WT mice but also had fewer branches and terminal duct tips and were deficient in production of secretory proteins. The p44/WDR77-null prostate tissue was less differentiated and hyperproliferative relative to WT littermates. In addition, the altered expression of androgen-regulated genes was observed in the p44/WDR77-null prostate. Thus, these results suggest that the AR cofactor p44/WDR77 plays important roles in prostate growth and differentiation by modulating AR-target gene expression.

PRL Signal Transduction in the Epithelial Compartment of Rat Prostate Maintained as Long-Term Organ Cultures in Vitro

Using long-term organ cultures of rat prostate tissue explants, we previously demonstrated that PRL both stimulates proliferation and acts as an androgen-independent suppressor of apoptosis in prostate epithelial cells, leading to epithelial hyperplasia. In this work we delineate intracellular signaling molecules activated by PRL in prostate tissue to identify candidate signaling proteins that are responsible for maintaining survival and proliferation of prostate epithelium in androgen-deprived growth environment. We now show that signal transducer and activator of transcription-5a (Stat5a) and Stat5b become tyrosine phosphorylated in response to PRL stimulation in rat prostate using prostate organ culture as an experimental model. Stat5 was translocated to the nuclei of epithelial cells of prostate tissue as demonstrated by immunohistochemistry. Furthermore, EMSA showed PRL-inducible binding of Stat5a homodimers and Stat5a/5b heterodimers to the PRL response element of the β-casein gene promoter. Signaling molecules Stat3, Stat1, MAPK, or protein kinase B, which can be activated by PRL in other target cells, were not activated by PRL in prostate tissue. Furthermore, we show that Stat5a and Stat5b are continuously phosphorylated in rat prostate in vivo, although they are expressed to varying degree in separate lobes of rat prostate. Collectively, our results suggest that PRL signaling in rat prostate tissue is primarily transduced via Stat5a and Stat5b. The Stat5 pathway represents one candidate signaling mechanism, used by PRL and possibly other growth factors and cytokines, that supports the viability of prostate epithelial cells during long-term androgen deprivation.

PRL Signal Transduction in the Epithelial Compartment of Rat Prostate Maintained as Long-Term Organ Cultures in Vitro

Using long-term organ cultures of rat prostate tissue explants, we previously demonstrated that PRL both stimulates proliferation and acts as an androgen-independent suppressor of apoptosis in prostate epithelial cells, leading to epithelial hyperplasia. In this work we delineate intracellular signaling molecules activated by PRL in prostate tissue to identify candidate signaling proteins that are responsible for maintaining survival and proliferation of prostate epithelium in androgen-deprived growth environment. We now show that signal transducer and activator of transcription-5a (Stat5a) and Stat5b become tyrosine phosphorylated in response to PRL stimulation in rat prostate using prostate organ culture as an experimental model. Stat5 was translocated to the nuclei of epithelial cells of prostate tissue as demonstrated by immunohistochemistry. Furthermore, EMSA showed PRL-inducible binding of Stat5a homodimers and Stat5a/5b heterodimers to the PRL response element of the beta-casein gene promoter. Signaling molecules Stat3, Stat1, MAPK, or protein kinase B, which can be activated by PRL in other target cells, were not activated by PRL in prostate tissue. Furthermore, we show that Stat5a and Stat5b are continuously phosphorylated in rat prostate in vivo, although they are expressed to varying degree in separate lobes of rat prostate. Collectively, our results suggest that PRL signaling in rat prostate tissue is primarily transduced via Stat5a and Stat5b. The Stat5 pathway represents one candidate signaling mechanism, used by PRL and possibly other growth factors and cytokines, that supports the viability of prostate epithelial cells during long-term androgen deprivation.

The proliferation of prostatic epithelium in chronic prostatitis.

The labelling index in chronic nonspecific prostatitis ranges from 0.7-2.1%. This value is markedly higher than in nodular hyperplasia (0.4%) as well as in differentiated adenocarcinomas (0.6%). Increased labelling index could only be determined in glands adjacent to inflammatory foci. In recognition of these findings we believe that a correct evaluation of the cell proliferation in chronic prostatitis is only possible if each single cell can be evaluated, whether it is altered by inflammation or not. Therefore, solid tissue biopsies appear to be more suitable in autroadiographical studies than cytological material alone.