UroToday - Following androgen deprivation, the prostate involutes, but can completely regenerate upon androgen restoration. Experiments that cycle androgen deprivation/restoration in rodents demonstrate that a population of self-renewable stem cells is responsible for survival of the prostate gland. In the January 31, 2006 issue of Proceeding of the National Academy of Sciences, Dr. Wang and colleagues from UCLA report their findings regarding prostate stem cells.
Their research team used the Pten-null murine model. PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor gene often mutated in human cancers. In this model, PTEN is deleted and the mouse prostate undergoes initiation and progression to prostatic intraepithelial neoplasia (PIN) and prostate cancer. PTEN negatively regulates basal cell proliferation and the authors found that Pten deletion in the basal cells leads to expansion of the Sca-1+ and BCL-2+stem/progenitor cells with differentiation. These findings support an important role for basal cells in the early initiation of prostate cancer.
The Pten knockout mice developed were verified to have Pten deletion in both the basal and luminal epithelial cell compartments and developed prostate cancer with pathological changes similar to human disease. Basal cells were identified using a series of cell markers and immunofluorescence microscopy. The basal cell population found to proliferate as the model progressed to prostate cancer and metastatic disease. The basal cells, however, were found to still retain their ability to differentiate.
Sca-1 is a cell surface antigen that is found in a subpopulation of cells in the prostate that have enhanced regenerative capacity and increased susceptibility to transformation to an oncogenic phenotype. These cells are enriched near the proximal region of the murine prostate ducts. In the Pten deleted prostate model, Sca-1+ cells were found to be increased 10-fold as the model progressed to PIN. Molecular analysis of these isolated cells demonstrated expression of markers found in basal cells, linking these two cell populations. Thus, both cell lineage and cell surface markers demonstrate the progressive cellular changes that occur during prostate cancer initiation and progression in the Pten
knockout mouse model.
By Christopher P. Evans, MD
PNAS 2006; 103; 1480-5
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