RGD Reference Report - BRAF activation initiates but does not maintain invasive prostate adenocarcinoma. - Rat Genome Database

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BRAF activation initiates but does not maintain invasive prostate adenocarcinoma.

Authors: Jeong, JH  Wang, Z  Guimaraes, AS  Ouyang, X  Figueiredo, JL  Ding, Z  Jiang, S  Guney, I  Kang, GH  Shin, E  Hahn, WC  Loda, MF  Abate-Shen, C  Weissleder, R  Chin, L 
Citation: Jeong JH, etal., PLoS One. 2008;3(12):e3949. Epub 2008 Dec 16.
RGD ID: 2315868
Pubmed: PMID:19079609   (View Abstract at PubMed)
PMCID: PMC2597248   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0003949   (Journal Full-text)

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 BRAF(V600E)--a mutation found in approximately 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 BRAF(V600E) in established prostate tumors did not lead to tumor regression, indicating that while sufficient to initiate development of invasive prostate adenocarcinoma, BRAF(V600E) is not required for its maintenance.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate adenocarcinoma  IMP 2315868 RGD 
prostate adenocarcinoma  ISOBRAF (Homo sapiens)2315868; 2315868 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Braf  (B-Raf proto-oncogene, serine/threonine kinase)

Genes (Mus musculus)
Braf  (Braf transforming gene)

Genes (Homo sapiens)
BRAF  (B-Raf proto-oncogene, serine/threonine kinase)


Additional Information