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Role of MAPK Activation in Prostate Cancer Development and Progression

Role of MAPK Activation in Prostate Cancer Development and Progression

Authors :
DANA-FARBER CANCER INST BOSTON MA
Jeong, Hyeong-nam
DANA-FARBER CANCER INST BOSTON MA
Jeong, Hyeong-nam
Source :
DTIC
Publication Year :
2008

Abstract

Although Prostate cancer is the most common and second leading cause of cancer-related deaths in American men lack of animal models that faithfully recapitulate histopathological and clinical features of human prostate cancer has hampered prostate cancer research. Taking advantage of a unique androgen-insensitive transgene promoter system we developed a novel genetically-engineered mouse (GEM) model of invasive prostate adenocarcinoma whereby an activating mutation of BRAFV600E has been targeted to the epithelial compartment of the prostate gland. As a first step for the characterization of this model we attempted to assess the requirement for continuous BRAF*-ERK activation in maintenance of established invasive lesions and in progression to androgen-independent state. To our surprise we found that while sufficient to initiate development of AKT-independent invasive prostate adenocarcinoma BRAFV600E is not required for its maintenance. In addition we also demonstrated that BRAF driven ERK and S6K activation alone is not sufficient to drive androgen-independent growth post castration in this mouse model although it appears to be permissive of survival in low androgen state.<br />The original document contains color images.

Details

Database :
OAIster
Journal :
DTIC
Notes :
text/html, English
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn832023001
Document Type :
Electronic Resource