Retinoic acid induces prostatic bud formation

Vezina, Chad M.; Allgeier, Sarah H.; Fritz, Wayne A.; Moore, Robert W.; Strerath, Michael; Bushman, Wade; Peterson, Richard E.

doi:10.1002/dvdy.21526

Cited by 43 publications

(52 citation statements)

References 85 publications

(93 reference statements)

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“…Only the assembly of Cx32 into GJs appeared to be significantly facilitated by 9-CRA and ATRA as neither the assembly nor degradation of adherens junction associated proteins, E-cadherin and α and β catenin, were significantly affected although the assembly of tight junction associated protein, occludin, appeared to be enhanced. The significance of these findings is further underscored by the fact that both androgens and retinoids have been documented to maintain the polarized and differentiated state of epithelial cells of normal prostate and prostatic tumors [19], [42]–[45], and all have been shown to have pleiotypic effects by acting as transcription factors [1], [3], [5], [46]. Our findings also showed that Cx32 expression potentiated the growth inhibitory effect of androgens and retinoids in LNCaP-32 cells, which indicates that their growth inhibitory and chemopreventive effects in prostate might be related to their ability to induce GJ formation.…”

Section: Discussionmentioning

confidence: 99%

Retinoids Regulate the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells

Kelsey¹,

Katoch²,

Johnson³

et al. 2012

PLoS ONE

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The retinoids, the natural or synthetic derivatives of Vitamin A (retinol), are essential for the normal development of prostate and have been shown to modulate prostate cancer progression in vivo as well as to modulate growth of several prostate cancer cell lines. 9-cis-retinoic acid and all-trans-retinoic acid are the two most important metabolites of retinol. Gap junctions, formed of proteins called connexins, are ensembles of intercellular channels that permit the exchange of small growth regulatory molecules between adjoining cells. Gap junctional communication is instrumental in the control of cell growth. We examined the effect of 9-cis-retinoic acid and all-trans retinoic acid on the formation and degradation of gap junctions as well as on junctional communication in an androgen-responsive prostate cancer cell line, LNCaP, which expressed retrovirally introduced connexin32, a connexin expressed by the luminal cells and well-differentiated cells of prostate tumors. Our results showed that 9-cis-retinoic acid and all-trans retinoic acid enhanced the assembly of connexin32 into gap junctions. Our results further showed that 9-cis-retinoic acid and all-trans-retinoic acid prevented androgen-regulated degradation of gap junctions, post-translationally, independent of androgen receptor mediated signaling. Finally, our findings showed that formation of gap junctions sensitized connexin32-expressing LNCaP cells to the growth modifying effects of 9-cis-retinoic acid, all-trans-retinoic acid and androgens. Thus, the effects of retinoids and androgens on growth and the formation and degradation of gap junctions and their function might be related to their ability to modulate prostate growth and cancer.

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Section: Discussionmentioning

confidence: 99%

Retinoids Regulate the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells

Kelsey¹,

Katoch²,

Johnson³

et al. 2012

PLoS ONE

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“…Pregnant dams were euthanized by CO2 asphyxiation and UGS tissue collected from resulting fetuses. For tissue separations 14 and 17 dpc UGS mesenchyme was enzymatically and mechanically separated from UGS epithelium and homogenized as described previously (22). …”

Section: Methodsmentioning

confidence: 99%

Androgen receptor DNA methylation regulates the timing and androgen sensitivity of mouse prostate ductal development

Keil

Abler

Laporta

et al. 2014

Developmental Biology

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Androgen receptor (AR) signaling initiates mouse prostate development by stimulating prostate ductal bud formation and specifying bud patterns. Curiously, however, prostatic bud initiation lags behind the onset of gonadal testosterone synthesis by about three days. This study’s objective was to test the hypothesis that DNA methylation controls the timing and scope of prostate ductal development by regulating Ar expression in the urogenital sinus (UGS) from which the prostate derives. We determined that Ar DNA methylation decreases in UGS mesenchyme during prostate bud formation in vivo and that this change correlates with decreased DNA methyltransferase expression in the same cell population during the same time period. To examine the role of DNA methylation in prostate development, fetal UGSs were grown in serum-free medium and 5 alpha dihydrotestosterone (DHT) and the DNA methylation inhibitor 5’-aza-2’-deoxycytidine (5AzadC) were introduced into the medium at specific times. As a measure of prostate development, in situ hybridization was used to visualize and count Nkx3-1 mRNA positive prostatic buds. We determined that inhibiting DNA methylation when prostatic buds are being specified, accelerates the onset of prostatic bud development, increases bud number, and sensitizes the budding response to androgens. Inhibition of DNA methylation also reduces Ar DNA methylation in UGS explants and increases Ar mRNA and protein in UGS mesenchyme and epithelium. Together, these results support a novel mechanism whereby Ar DNA methylation regulates UGS androgen sensitivity to control the rate and number of prostatic buds formed, thereby establishing a developmental checkpoint.

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“…The prostate gland is an out pouching of the posterior endoderm and RA is both necessary and sufficient for the formation of prostatic buds [140]. Fgf10 is also essential for budding of the prostate [141].…”

Section: Retinoic Acid and Posterior Endodermmentioning

confidence: 99%

Retinoic Acid and the Development of the Endoderm

Kelly

Drysdale

2015

JDB

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Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of the embryo proper.

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Retinoic acid induces prostatic bud formation

Cited by 43 publications

References 85 publications

Retinoids Regulate the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells

Retinoids Regulate the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells

Androgen receptor DNA methylation regulates the timing and androgen sensitivity of mouse prostate ductal development

Retinoic Acid and the Development of the Endoderm

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