BRAF activation initiates but does not maintain invasive prostate adenocarcinoma

Joseph H. Jeong, Zhenxiong Wang, Alexander S. Guimaraes, Xuesong Ouyang, Jose L. Figueiredo, Zhihu Ding, Shan Jiang, Isil Guney, Gyeong Hoon Kang, Eyoung Shin, William C. Hahn, Massimo F. Loda, Cory Abate-Shen, Ralph Weissleder, Lynda Chin

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Article numbere3949
JournalPloS one
Volume3
Issue number12
DOIs
StatePublished - Dec 16 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Jeong, J. H., Wang, Z., Guimaraes, A. S., Ouyang, X., Figueiredo, J. L., Ding, Z., Jiang, S., Guney, I., Kang, G. H., Shin, E., Hahn, W. C., Loda, M. F., Abate-Shen, C., Weissleder, R., & Chin, L. (2008). BRAF activation initiates but does not maintain invasive prostate adenocarcinoma. PloS one, 3(12), [e3949]. https://doi.org/10.1371/journal.pone.0003949