Bisphenol A Promotes Human Prostate Stem-Progenitor Cell Self-Renewal and Increases In ... - 0 views
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these findings show that estrogen stimulates human prostate epithelial stem cell self-renewal and progenitor cell amplification (prostasphere size), with the greatest effects observed at lower E2 doses.
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Similar to E2, BPA increased prostasphere number and size with significant and maximal effects observed at 10 nM BPA
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Taken together, these results provide strong evidence that, similar to E2, BPA increases stem cell self-renewal and progenitor amplification in normal human prostate epithelial cells
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these findings provide further support that E2 and BPA maintain the stem-like state within the normal prostate epithelial cell population
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Our previous findings demonstrated that normal prostate stem-progenitor cells within the prostaspheres expressed ERα and ERβ, implicating them as direct targets for E2 and BPA action
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BPA and E2 had equimolar capacity for activation of these rapid signaling pathways in human prostaspheres, thus identifying a dynamic and robust signaling pathway initiated by low-dose BPA exposure in prostate stem-progenitor cells.
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these findings indicate that both rapid membrane-initiated estrogen action and genomic ER signaling pathways are operative in human prostate progenitor cells.
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these results document the fact that levels of bioactive BPA in the present study are similar to levels found in human umbilical cord blood and newborns in the general population
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the present findings identify for the first time that in vivo exposure of the human prostate epithelium to low doses of BPA significantly increases the susceptibility of the human prostate epithelium to hormonal carcinogenesis.
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The current study provides clear evidence that, similar to E2, normal human prostate stem and progenitor cells are direct targets for BPA action
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Both hormones increased stem-like cell numbers in primary prostate epithelial cultures in a dose-dependent manner and augmented the number and size of 3-D cultured prostaspheres, markers of stem cell self-renewal and progenitor cell proliferation, respectively
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signaling pathways engaged by estrogens through these separate receptors are multiple and complex, including both membrane-initiated signaling and genomic activation via ER transcriptional activity
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the current results indicate that developmental exposure to BPA, at doses routinely found in humans, significantly increases the cancer risk in human prostate epithelium in response to elevated estrogen levels in an androgen-supported milieu. Because relative estrogen levels rise in aging men, we suggest that humans may be susceptible to BPA-driven prostate disease in a manner similar to that in the rodent models.
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We propose that early-life perturbations in estrogen signaling including inappropriate exposure to BPA have the potential to amplify and modify the stem-progenitor cell populations within the human prostate gland and, in so doing, alter the normal homeostatic mechanisms that maintain a growth neutral state throughout life