Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation.
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.
Wang
Shunyou
S
Departments of Molecular and Medical Pharmacology and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California-Los Angeles, 650 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Garcia
Alejandro J
AJ
Wu
Michelle
M
Lawson
Devon A
DA
Witte
Owen N
ON
Wu
Hong
H
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; D001973:Bromodeoxyuridine