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Stromal TGF-β signaling induces AR activation in prostate cancer

Overview of attention for article published in Oncotarget, October 2014
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Title
Stromal TGF-β signaling induces AR activation in prostate cancer
Published in
Oncotarget, October 2014
DOI 10.18632/oncotarget.2536
Pubmed ID
Authors

Feng Yang, Yizhen Chen, Tao Shen, Dan Guo, Olga Dakhova, Michael M. Ittmann, Chad J. Creighton, Yiqun Zhang, Truong D. Dang, David R. Rowley

Abstract

AR signaling is essential for the growth and survival of prostate cancer (PCa), including most of the lethal castration-resistant PCa (CRPC). We previously reported that TGF-β signaling in prostate stroma promotes prostate tumor angiogenesis and growth. By using a PCa/stroma co-culture model, here we show that stromal TGF-β signaling induces comprehensive morphology changes of PCa LNCaP cells. Furthermore, it induces AR activation in LNCaP cells in the absence of significant levels of androgen, as evidenced by induction of several AR target genes including PSA, TMPRSS2, and KLK4. SD-208, a TGF-β receptor 1 specific inhibitor, blocks this TGF-β induced biology. Importantly, stromal TGF-β signaling together with DHT induce robust activation of AR. MDV3100 effectively blocks DHT-induced, but not stromal TGF-β signaling induced AR activation in LNCaP cells, indicating that stromal TGF-β signaling induces both ligand-dependent and ligand-independent AR activation in PCa. TGF-β induces the expression of several growth factors and cytokines in prostate stromal cells, including IL-6, and BMP-6. Interestingly, BMP-6 and IL-6 together induces robust AR activation in these co-cultures, and neutralizing antibodies against BMP-6 and IL-6 attenuate this action. Altogether, our study strongly suggests tumor stromal microenvironment induced AR activation as a direct mechanism of CRPC.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Denmark 1 2%
Slovenia 1 2%
Unknown 43 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 33%
Student > Bachelor 9 20%
Researcher 6 13%
Student > Master 5 11%
Student > Doctoral Student 4 9%
Other 2 4%
Unknown 5 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 24%
Agricultural and Biological Sciences 10 22%
Medicine and Dentistry 10 22%
Nursing and Health Professions 2 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 3 7%
Unknown 9 20%