Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 39, Pages 16392-16397Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1101263108
Keywords
ErbB2; PI3K; mouse models
Categories
Funding
- Cancer Research UK
- Medical Research Council
- Cancer Research UK [15151, 12481] Funding Source: researchfish
- Medical Research Council [G0802141, G0900871] Funding Source: researchfish
- MRC [G0900871, G0802141] Funding Source: UKRI
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Prostate cancer (CaP) is the most common cancer among adult men in the Western world. Better insight into its tumor-activating pathways may facilitate the development of targeted therapies. In this study, we show that patients who develop prostate tumors with low levels of PTEN and high levels of HER2/3 have a poor prognosis. This is functionally relevant, as targeting Her2 activation to the murine prostate cooperates with Pten loss and drives CaP progression. Mechanistically, this is associated with activation of the MAPK pathway and abrogation of the Pten loss-induced cellular senescence program. Importantly, inhibition of MEK function strongly suppressed proliferation within these tumors by restoring the Pten loss-induced cellular senescence program. Taken together, these data suggest that stratification of CaP patients for HER2/3 and PTEN status could identify patients with aggressive CaP who may respond favorably to MEK inhibition.
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