ORCID Profile
0000-0002-6059-6550
Current Organisation
NorthShore University HealthSystem
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Publisher: Wiley
Date: 09-2010
DOI: 10.1002/PROS.21244
Publisher: CSIRO Publishing
Date: 2001
DOI: 10.1071/RD01010
Abstract: Estrogens, alone or in combination with androgens, can induce aberrant growth and/or malignancy of the prostate gland. Squamous metaplasia is an abnormal form of prostatic epithelial differentiation elicited by exogenous estrogen alone. Estrogens elicit their effects via estrogen receptors (ER) in the prostate. Experiments using ERα and ERβ null mice demonstrated that ERα, but not ERβ is essential in the induction of prostatic squamous metaplasia. To determine the respective roles of epithelial versus stromal ERα in this response, the following tissue recombinants were constructed with prostatic epithelium (PRE) and stroma (S) from wild-type (wt) and ERα knockout (αERKO) mice: wt-S + wt-PRE, · αERKO-S + αERKO-PRE, wt-S + αERKO-PRE and αERKO-S + wt-PRE. A metaplastic response to diethylstilbestrol (DES) was only observed in wt-S + wt-PRE tissue recombinants. Tissue recombinants containing αERKO-PRE and/or αERKO-S (ERKO-S + αERKO-PRE, wt-S + αERKO-PRE and αERKO-S + wt-PRE) failed to respond to DES. Therefore, full and uniform epithelial squamous metaplasia requires ERα in both the epithelium and stroma. Estradiol (E2) in combination with testosterone (T) was shown to be effective in inducing prostatic carcinogenesis in a tissue recombinant model composed of rat urogenital sinus mesenchyme plus mouse prostatic epithelium. A particularly efficient model of prostatic carcinogenesis in mice involves T + E2 treatment of mice bearing grafts of wild-type rat urogenital mesenchyme (rUGM) plus retinoblastoma gene (Rb) knockout (Rb-KO) prostatic epithelium (rUGM + Rb-KO-PRE). Such rUGM + Rb-KO-PRE tissue recombinants developed hyperplasia, atypical hyperplasia and invasive prostatic carcinoma with high efficiency. During carcinogenesis in rUGM + Rb-KO-PRE tissue recombinants, epithelial E-cadherin almost totally disappeared and epithelial PCNA labeling was elevated. These epithelial changes were associated with almost total loss of smooth muscle cells in the stroma. The results of this study demonstrate that the absence of the Rb tumor suppressor gene predisposes prostatic epithelial cells to hormonal carcinogenesis.
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.JSBMB.2004.10.017
Abstract: This review on normal and neoplastic growth of the prostate emphasizes the importance of epithelial-mesenchymal/stromal interactions. Accordingly, during prostatic development urogenital sinus mesenchyme (a) specifies prostatic epithelial identity, (b) induces epithelial bud formation, (c) elicits prostatic bud growth and regulates ductal branching, (d) promotes differentiation of a secretory epithelium, and (e) specifies the types of secretory proteins expressed. In reciprocal fashion, prostatic epithelium induces smooth muscle differentiation in the mesenchyme. Epithelial-mesenchymal interactions during development continue postnatally into adulthood as stromal-epithelial interactions which play a homeostatic role and in so doing reciprocally maintain epithelial and stromal differentiation and growth-quiescence. Prostatic carcinogenesis involves perturbation of these reciprocal homeostatic cell-cell interactions. The central role of mesenchyme in prostatic epithelial development has been firmly established through analysis of tissue recombinants composed of androgen-receptor-positive wild-type mesenchyme and androgen-receptor-negative epithelium. These studies revealed that at the very least ductal morphogenesis, epithelial cytodifferentiation, epithelial apoptosis and epithelial proliferation are regulated by stromal and not epithelial androgen receptors. Likewise, progression from non-tumorigenesis to tumorigenesis elicited by testosterone plus estradiol proceeds via paracrine mechanisms. Thus, stromal-epithelial interactions play critical roles in the hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United States of America
No related grants have been discovered for Simon Hayward.