Abstract
PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined cell lineage markers, we demonstrate that PTEN negatively regulates p63-positive prostatic basal cell proliferation without blocking differentiation. Concomitant with basal cell proliferation is the expansion of a prostate stem/progenitor-like subpopulation as evidenced by the progressive increase of stem cell antigen-1 (Sca-1)- and BCL-2-positive cells. This observation provides strong evidence that basal cell proliferation can be an initiating event for precancerous lesions. Sca-1(+) and BCL-2(+) progenitors may serve as cancer-initiating cells in this model.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
Bromodeoxyuridine / pharmacology
-
Cell Differentiation
-
Cell Line, Tumor
-
Cell Nucleus / metabolism
-
Cell Proliferation
-
Cell Separation
-
DNA-Binding Proteins
-
Disease Models, Animal
-
Disease Progression
-
Flow Cytometry
-
Gene Deletion
-
Genes, Tumor Suppressor
-
Humans
-
Immunohistochemistry
-
Ki-67 Antigen / biosynthesis
-
Kinetics
-
Male
-
Mice
-
Mice, Knockout
-
Microscopy, Fluorescence
-
Neoplasms / metabolism
-
PTEN Phosphohydrolase / metabolism
-
PTEN Phosphohydrolase / physiology*
-
Phosphoproteins / metabolism
-
Prostatic Neoplasms / genetics*
-
Prostatic Neoplasms / pathology
-
Stem Cells / cytology*
-
Time Factors
-
Trans-Activators / metabolism
-
Transcription Factors
-
Tumor Suppressor Proteins
Substances
-
DNA-Binding Proteins
-
Ki-67 Antigen
-
Phosphoproteins
-
TP63 protein, human
-
Trans-Activators
-
Transcription Factors
-
Trp63 protein, mouse
-
Tumor Suppressor Proteins
-
PTEN Phosphohydrolase
-
Bromodeoxyuridine