BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma

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BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma

Show simple item record Jeong, Joseph H. Wang, Zhenxiong Ouyang, Xuesong Jiang, Shan Guney, Isil Kang, Gyeong Hoon Abate-Shen, Cory Guimaraes, Alexander Savio Ramos Figueiredo, Jose L. Ding, Zhihu Shin, Eyoung Hahn, William C. Loda, Massimo Weissleder, Ralph Chin, Lynda 2011-10-25T14:36:23Z 2008
dc.identifier.citation 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. en_US
dc.identifier.issn 1932-6203 en_US
dc.description.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. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0003949 en_US
dc.relation.hasversion en_US
dash.license LAA
dc.subject molecular biology en_US
dc.subject oncology en_US
dc.subject prostate cancer en_US
dc.subject urology en_US
dc.title BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US Guimaraes, Alexander Savio Ramos 2011-10-25T14:36:23Z
dash.affiliation.other HMS^Microbiology and Molecular Genetics en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Radiology-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Systems Biology en_US
dash.affiliation.other HMS^Dermatology-Brigham and Women's Hospital en_US

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