BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma
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Author
Jeong, Joseph H.
Wang, Zhenxiong
Ouyang, Xuesong
Jiang, Shan
Guney, Isil
Kang, Gyeong Hoon
Abate-Shen, Cory
Shin, Eyoung
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0003949Metadata
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Jeong, Joseph H., Zhenxiong Wang, Alexander S. Guimaraes, Xuesong Ouyang, Jose L. Figueiredo, Zhihu Ding, Shan Jiang, et al. 2008. BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma. PLoS ONE 3(12): e3949.Abstract
Prostate cancer is the second leading cause of cancer-related deaths in men. Activation of MAP kinase signaling pathway has been implicated in advanced and androgen-independent prostate cancers, although formal genetic proof has been lacking. In the course of modeling malignant melanoma in a tyrosinase promoter transgenic system, we developed a genetically-engineered mouse (GEM) model of invasive prostate cancers, whereby an activating mutation of BRAFV600E–a mutation found in ∼10% of human prostate tumors–was targeted to the epithelial compartment of the prostate gland on the background of Ink4a/Arf deficiency. These GEM mice developed prostate gland hyperplasia with progression to rapidly growing invasive adenocarcinoma without evidence of AKT activation, providing genetic proof that activation of MAP kinase signaling is sufficient to drive prostate tumorigenesis. Importantly, genetic extinction of BRAFV600E in established prostate tumors did not lead to tumor regression, indicating that while sufficient to initiate development of invasive prostate adenocarcinoma, BRAFV600E is not required for its maintenance.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597248/pdf/Terms of Use
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