期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 6, 页码 2610-2615出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0913873107
关键词
AKT; AR; ETS; ERG; CD49f
资金
- Prostate Cancer Foundation
- National Institutes of Health [5 K12 HD001400, 1K99/R00 CA125937]
- Ovarian Cancer Research Fund
- University of California Los Angeles
- Stein/Oppenheimer Clinical Translational Seed Grant
- American Cancer Society [RSG-07-092-01-TBE]
- Department of Defense Prostate Cancer Research [PC061456]
Prevailing theories suggest that luminal cells are the origin of prostate cancer because it is histologically defined by basal cell loss and malignant luminal cell expansion. We introduced a series of genetic alterations into prospectively identified populations of murine basal/stem and luminal cells in an in vivo prostate regeneration assay. Stromal induction of FGF signaling, increased expression of the ETS family transcription factor ERG1, and constitutive activation of PI3K signaling were evaluated. Combination of activated PI3K signaling and heightened androgen receptor signaling, which is associated with disease progression to androgen independence, was also performed. Even though luminal cells fail to respond, basal/stem cells demonstrate efficient capacity for cancer initiation and can produce luminal-like disease characteristic of human prostate cancer in multiple models. This finding provides evidence in support of basal epithelial stem cells as one target cell for prostate cancer initiation and demonstrates the propensity of primitive cells for tumorigenesis.
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