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  E-mail Message: I thought you might be interested in this item at http://www.worldcat.org/oclc/465322352 Title: Identify the Impact of TGF-Beta Signaling on the Stroma in the Progression of Prostate Cancer. Author: Neil A Bhowmick; VANDERBILT UNIV NASHVILLE TN Publisher: Ft. Belvoir : Defense Technical Information Center, 01 MAR 2008. OCLC:465322352

  
  

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Subjects

• Anatomy and physiology.
• Medicine and medical research.
• Epithelium.
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Identify the Impact of TGF-Beta Signaling on the Stroma in the Progression of Prostate Cancer.

Author:	Neil A Bhowmick; VANDERBILT UNIV NASHVILLE TN.
Publisher:	Ft. Belvoir : Defense Technical Information Center, 01 MAR 2008.
Edition/Format:	Book : EnglishView all editions and formats
Summary:	As a result of androgen ablation TGF- 1 expression levels transiently elevate and regression of benign prostate hyperplasia as well as prostate cancer cells for the most part occur. Better understanding of prostate androgen responsiveness is critical in understanding and ultimately combating androgen-non-responsive prostate cancer. Studying the conditional TGF- type II receptor fibroblast knockout mouse model we developed (F KO), we found that TGF- signaling in the prostate stromal fibroblasts regulate both stromal and epithelial differentiation in the prostate. As proposed we attempted to develop mice that are stromally knocked out for TGF- signaling and express the large T antigen in the prostate epithelia, but was unsuccessful. Thus we made tissue recombinants of prostatic epithelia with F KO stromal cells. This resulted in the development of poorly differentiated adenocarcinoma compared to when the same epithelia was combined with control stromal cells. Moreover, we found that the F KO associated epithelia was refractile to androgen ablation. The mechanism of these observations seems to be due to stromally derived paracrine Wnt5a activating the epithelial frizzled receptor 2 that enabled prostate epithelial survival in an androgen deficient environment. We hope to gain permission to progress with these experiments to further address the mechanism of stromal TGF- signaling impact on prostate cancer androgen responsiveness and differentiation.  Read more...
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