scholarly journals Wnt Inhibitory Factor 1 (Wif1) Is Regulated by Androgens and Enhances Androgen-Dependent Prostate Development

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 6091-6103 ◽  
Author(s):  
Kimberly P. Keil ◽  
Vatsal Mehta ◽  
Amanda M. Branam ◽  
Lisa L. Abler ◽  
Rita A. Buresh-Stiemke ◽  
...  
Keyword(s):  
Branching Morphogenesis ◽  
Inhibitory Factor ◽  
Urogenital Sinus ◽  
Sexually Dimorphic ◽  
Bud Formation ◽  
Prostate Development ◽  
Mouse Prostate ◽  
Necessary And Sufficient ◽  
Wnt Inhibitory Factor 1 ◽  
Inhibitory Factor 1

Abstract Fetal prostate development from urogenital sinus (UGS) epithelium requires androgen receptor (AR) activation in UGS mesenchyme (UGM). Despite growing awareness of sexually dimorphic gene expression in the UGS, we are still limited in our knowledge of androgen-responsive genes in UGM that initiate prostate ductal development. We found that WNT inhibitory factor 1 (Wif1) mRNA is more abundant in male vs. female mouse UGM in which its expression temporally and spatially overlaps androgen-responsive steroid 5α-reductase 2 (Srd5a2). Wif1 mRNA is also present in prostatic buds during their elongation and branching morphogenesis. Androgens are necessary and sufficient for Wif1 expression in mouse UGS explant mesenchyme, and testicular androgens remain necessary for normal Wif1 expression in adult mouse prostate stroma. WIF1 contributes functionally to prostatic bud formation. In the presence of androgens, exogenous WIF1 protein increases prostatic bud number and UGS basal epithelial cell proliferation without noticeably altering the pattern of WNT/β-catenin-responsive Axin2 or lymphoid enhancer binding factor 1 (Lef1) mRNA. Wif1 mutant male UGSs exhibit increased (Sfrp)2 and (Sfrp)3 expression and form the same number of prostatic buds as the wild-type control males. Collectively our results reveal Wif1 as one of the few known androgen-responsive genes in the fetal mouse UGM and support the hypothesis that androgen-dependent Wif1 expression is linked to the mechanism of androgen-induced prostatic bud formation.

scholarly journals Sulfatase 1 Is an Inhibitor of Ductal Morphogenesis with Sexually Dimorphic Expression in the Urogenital Sinus

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3420-3431 ◽  
Author(s):  
Rita A. Buresh ◽  
Sheri L. Kuslak ◽  
Melissa A. Rusch ◽  
Chad M. Vezina ◽  
Scott B. Selleck ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Branching Morphogenesis ◽  
Urogenital Sinus ◽  
Sexually Dimorphic ◽  
Ductal Morphogenesis ◽  
Prostate Development ◽  
Sexually Dimorphic Expression ◽  
Dimorphic Expression

The prostate gland develops from the urogenital sinus in response to circulating androgens. Androgens initiate and stimulate branching morphogenesis in the urogenital sinus via unknown mediators. Heparan sulfate proteoglycans are important extracellular molecules that sequester many growth factors in the extracellular matrix and facilitate signaling by some growth factors as part of ternary complexes that include growth factors, receptors, and heparan sulfate chains. Several enzymes modify the chemical structure of heparan sulfate to further regulate its activity. An examination of these enzymes for sexually dimorphic expression in the urogenital sinus identified Sulfatase 1 (Sulf1) as an enzyme that was down-regulated in the male urogenital sinus coincident with the initiation of prostatic morphogenesis. Down-regulation of Sulf1 was accompanied by an increase in the most highly sulfated forms of heparan sulfate, and a similar increase was observed in female urogenital sinuses treated with testosterone. Inhibiting de novo sulfation of heparan sulfate blocked prostatic morphogenesis, supporting the importance of heparan sulfate modification for prostate development. To functionally test the specific role of Sulf1 during prostate development, Sulf1 was ectopically expressed in the urogenital sinus. It partially inhibited testosterone-stimulated ductal morphogenesis, and it reduced the activation of fibroblast growth factor receptors as well as the ERK1 and ERK2 MAPKs. These data identify sulfatase 1 as an inhibitor of prostatic branching morphogenesis and growth factor signaling that is down-regulated as part of the normal response to androgen action in the male urogenital sinus.

scholarly journals Promoter methylation of WNT inhibitory factor-1 may be associated with the pathogenesis of multiple human tumors

2018 ◽  
Vol 14 (9) ◽  
pp. 381 ◽  
Author(s):  
Jianliang Zhang ◽  
Yong Zhou ◽  
Zhaohua Li ◽  
Yinlu Ding ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Human Tumors ◽  
Inhibitory Factor ◽  
Wnt Inhibitory Factor 1 ◽  
Inhibitory Factor 1

144 HYPERMETHYLATION SILENCES WNT INHIBITORY FACTOR 1 IN NASOPHARYNGEAL CARCINOMA.

2006 ◽  
Vol 54 (1) ◽  
pp. S104.6-S105
Author(s):  
E. G. Thung ◽  
J. Chou ◽  
L. You ◽  
Z. Xu ◽  
D. M. Jablons
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Inhibitory Factor ◽  
Wnt Inhibitory Factor 1 ◽  
Inhibitory Factor 1

scholarly journals Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers

Oncogene ◽  
2005 ◽  
Vol 24 (53) ◽  
pp. 7946-7952 ◽  
Author(s):  
Hiroaki Taniguchi ◽  
Hiroyuki Yamamoto ◽  
Tamaki Hirata ◽  
Nobuki Miyamoto ◽  
Mariko Oki ◽  
...  
Keyword(s):  
Inhibitory Factor ◽  
Gastrointestinal Cancers ◽  
Epigenetic Inactivation ◽  
Wnt Inhibitory Factor 1 ◽  
Inhibitory Factor 1

scholarly journals Functional Significance of Wnt Inhibitory Factor-1 Gene in Kidney Cancer

2009 ◽  
Vol 69 (22) ◽  
pp. 8603-8610 ◽  
Author(s):  
K. Kawakami ◽  
H. Hirata ◽  
S. Yamamura ◽  
N. Kikuno ◽  
S. Saini ◽  
...  
Keyword(s):  
Kidney Cancer ◽  
Functional Significance ◽  
Inhibitory Factor ◽  
Wnt Inhibitory Factor 1 ◽  
Inhibitory Factor 1
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