scholarly journals TMPRSS2:ERG gene fusion variants induce TGF-β signaling and epithelial to mesenchymal transition in human prostate cancer cells

Oncotarget ◽  
2017 ◽  
Vol 8 (15) ◽  
pp. 25115-25130 ◽  
Author(s):  
Leonie Ratz ◽  
Mark Laible ◽  
Lukasz A. Kacprzyk ◽  
Stephanie M. Wittig-Blaich ◽  
Yanis Tolstov ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Gene Fusion ◽  
Epithelial To Mesenchymal Transition ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition

Effect of androgen signaling in stromal cells on growth of prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 297-297 ◽  
Author(s):  
Chun-Peng Liao ◽  
Leng-Ying Chen ◽  
Andrea Luethy ◽  
Youngsoo Kim ◽  
A. Robert MacLeod ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Culture System ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Epithelial Cancer ◽  
Mesenchymal Transition

297 Background: Interactions between epithelial and stroma cells are important in the development of prostate cancer (PCa). Cancer-associated fibroblasts (CAFs) have been to support tumor progression, metastasis, and differentiation. Androgen receptor (AR) and related pathways are known to support the growth and survival of prostate epithelial cancer cells, the roles of AR-dependent processes in cancerous stroma are less clear. We sought to investigate if AR-dependent pathways present in CAF cells influence the growth and tumorogencity of epithelial cancer cells in relation to androgen-deprivation therapy in prostate cancer. Methods: Murine CAFs were isolated from a well-described PTEN-dependent cancer mouse model (Liao, et al Cancer Res, 2010. 70(18):7294). A co-culture system was developed based on multiple lines of murine CAFs grown along with human prostate cancer epithelial cells, and a murine-specific anti-sense oligonucleotide (ASO) against murine AR was used to specifically suppress AR expression in murine CAFs in this system. RT-PCR was used to investigate changes in gene expression. Results: Using this co-culture system, we found that murine CAFs promoted cell proliferation and colony formation in several human prostate cancer cell lines. Further, these processes were decreased by suppression of AR-expression in CAFs. Expression of genes related to tumorigenicity in epithelial cells were investigated. Markers associated with epithelial-mesenchymal transition (EMT, N-Cad) and “stemness” (OCT4, Sox2, Nanog) were increased in human prostate cancer cells grown with low-AR CAFs. Conclusions: Our data indicates that suppression of AR in CAFs results in down-regulation in the growth and tumorigenicity of prostate cancer cells through pathways related to EMT and “cell reprograming”. As such, development of therapies which inhibit the tumor-promoting pathways present in stromal cells may be one approach to improve the treatment of prostate cancer.

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