Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate

Joesting, Margaret S.; Cheever, Thomas R.; Volzing, Katherine; Yamaguchi, Terry P.; Wolf, Vladimir; Näf, Dieter; Rubin, Jeffrey S.; Marker, Paul C.

doi:10.1016/j.ydbio.2008.02.021

Cited by 41 publications

(37 citation statements)

References 46 publications

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“…7). This mechanism is consistent with previous reports of paracrine signaling for secreted ligands of the WNT (Allgeier et al, 2008;Huang et al, 2009;Joesting et al, 2008;Keil et al, 2012), FGF (Alarid et al, 1994;Donjacour et al, 2003;Sugimura et al, 1996;Thomson and Cunha, 1999) and TGFβ (Cancilla et al, 2001;Cook Fig. 6.…”

Section: Paracrine Signaling Between the Inductive Urm And Pre Duringsupporting

confidence: 93%

“…Outgrowth of the PrE is dictated by time-specific and cell-specific expression of morphogenetic genes (Prins and Putz, 2008;Thomson and Marker, 2006), including secreted signaling ligands of the hedgehog (Berman et al, 2004;Doles et al, 2006;Freestone et al, 2003;Lamm et al, 2002;Podlasek et al, 1999;Pu et al, 2004;Wang et al, 2003), Wnt (Allgeier et al, 2008;Huang et al, 2009;Joesting et al, 2008;Keil et al, 2012), FGF (Alarid et al, 1994;Donjacour et al, 2003;Sugimura et al, 1996;Thomson and Cunha, 1999) and TGFβ (Cancilla et al, 2001;Cook et al, 2007;Grishina et al, 2005;Itoh et al, 1998;Lamm et al, 2001;Tanji et al, 1994;Tomlinson et al, 2004) gene super-families. These morphogens are thought to communicate autocrine and paracrine signals through their cognate receptors and downstream signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

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RET-mediated glial cell line derived neurotrophic factor signaling inhibits mouse prostate development

Park

Bolton

2017

Development

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In humans and rodents, the prostate gland develops from the embryonic urogenital sinus (UGS). The androgen receptor (AR) is thought to control the expression of morphogenetic genes in inductive UGS mesenchyme, which promotes proliferation and cytodifferentiation of the prostatic epithelium. However, the nature of the AR-regulated morphogenetic genes and the mechanisms whereby AR controls prostate development are not understood. Glial cell line-derived neurotrophic factor (GDNF) binds GDNF family receptor α1 (GFRα1) and signals through activation of RET tyrosine kinase. Gene disruption studies in mice have revealed essential roles for GDNF signaling in development; however, its role in prostate development is unexplored. Here, we establish novel roles of GDNF signaling in mouse prostate development. Using an organ culture system for prostate development and Ret mutant mice, we demonstrate that RET-mediated GDNF signaling in UGS increases proliferation of mesenchyme cells and suppresses androgen-induced proliferation and differentiation of prostate epithelial cells, inhibiting prostate development. We also identify Ar as a GDNF-repressed gene and Gdnf and Gfrα1 as androgen-repressed genes in UGS, thus establishing reciprocal regulatory crosstalk between AR and GDNF signaling in prostate development.

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Section: Paracrine Signaling Between the Inductive Urm And Pre Duringsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

RET-mediated glial cell line derived neurotrophic factor signaling inhibits mouse prostate development

Park

Bolton

2017

Development

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“…SFRP1 null prostates exhibited multiple developmental defects in the epithelium such as reduced branching morphogenesis, delayed proliferation, and increased expression of genes encoding prostate-specific secretory proteins. In contrast, over-expression of SFRP1 in the adult prostates of transgenic mice showed prolonged epithelial proliferation and decreased expression of the secretory genes 49 . Another antagonist of the Wnt pathway, SFRP2, was shown to be expressed on embryonic day 16.5 UGS and downregulated according to prostate maturation 50 .…”

Section: Role Of Wnt Signaling In Prostate Developmentmentioning

confidence: 87%

WNT Signaling in Prostate Development and Carcinogenesis

Kharaishvili¹,

Simkova²,

Makharoblidze³

et al. 2011

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. The Wnt signaling pathway is crucial for cell fate decisions, stem cell renewal, regulation of cell proliferation and differentiation. Deregulated Wnt signaling is also implicated in a number of hereditary and degenerative diseases and cancer.Methods and results. This review highlights the role of the Wnt pathway in the regulation of stem/progenitor cell renewal and prostate gland development and how this signaling is altered in prostate cancer. Recent evidence suggests that Wnt signaling regulates androgen activity in prostate cancer cells, enhances androgen receptor expression and promotes the growth of prostate cancer even after androgen ablation therapy. There is also strong evidence that Wnt signaling is enhanced in androgen-ablation resistant tumors and bone metastases.Conclusions. Further study of the modulators of this pathway will be of therapeutic relevance as inhibition of Wnt signaling may have the potential to reduce the self-renewal and aggressive behaviour of prostate cancer while Wnt signaling activation might enhance stem cell activity when tissue regeneration is required.

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“…Elevated levels of SFRP1 and other Wnt antagonists including SFRP2, SFRP4, Dickkopf 1, and Wnt-inhibitory factor-1 have been reported in various tumors (27,28,(31)(32)(33). SFRP1 overexpression has been observed in uterine leiomyomas (31) and prostate carcinoma-derived stromal cells (33).…”

Section: Discussionmentioning

confidence: 99%

Functional Significance of Secreted Frizzled-Related Protein 1 in Metastatic Renal Cell Carcinomas

et al. 2009

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The secreted Frizzled-related protein 1 (SFRP1) is a Winglesstype (Wnt) antagonist that has been associated with various malignancies, including renal cell carcinomas (RCC). However, the functional significance of SFRP1 has never been investigated in metastatic RCC. Here, we investigated the role of this molecule in kidney cancer progression and metastasis. Using Wnt pathway-focused cDNA expression profiling in normal renal, primary RCC, and metastatic RCC cell lines, we identified that SFRP1 is up-regulated in metastatic RCC. SFRP1 overexpression in metastatic RCC was confirmed by immunostaining in renal tissues. We explored the molecular mechanisms underlying SFRP1 up-regulation by analyzing DNA methylation and histone modification patterns on SFRP1 promoter. We found that this gene is unmethylated/hypomethylated and enriched in activating histone modifications in metastatic RCC. To understand the functional significance of SFRP1 overexpression in metastatic RCC with regard to tumorigenesis, we used a small interfering RNA-mediated approach to knockdown the gene and monitored cellular proliferation, apoptosis, and metastatic behavior. Proliferation was unaltered and apoptosis increased on attenuation of SFRP1 expression. Also, SFRP1 depletion decreased the invasive potential of the metastatic RCC cell line, suggesting that the overexpression of this Wnt antagonist may be related to invasiveness and metastatic behavior in RCC. We investigated the molecular basis of the role of SFRP1 in invasion and metastasis and found that matrix metalloproteinase MMP10 is regulated by SFRP1. In conclusion, our data suggest that SFRP1 plays a role in the metastatic potential of RCC. The present findings may be important in the design of treatment modalities for metastatic RCC. [Cancer Res 2009;69(17):6815-22]

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Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate

Cited by 41 publications

References 46 publications

RET-mediated glial cell line derived neurotrophic factor signaling inhibits mouse prostate development

RET-mediated glial cell line derived neurotrophic factor signaling inhibits mouse prostate development

WNT Signaling in Prostate Development and Carcinogenesis

Functional Significance of Secreted Frizzled-Related Protein 1 in Metastatic Renal Cell Carcinomas

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