p63 is a prostate basal cell marker and is required for prostate development.
The p53 homologue p63 encodes for different isotypes able to either transactivate p53 reporter genes (TAp63) or act as p53-dominant-negatives (DeltaNp63). p63 is expressed in the basal cells of many epithelial organs and its germline inactivation in the mouse results in agenesis of organs such as skin appendages and the breast. Here, we show that prostate basal cells, but not secretory or neuroendocrine cells, express p63. In addition, prostate basal cells in culture predominantly express the DeltaNp63alpha isotype. In contrast, p63 protein is not detected in human prostate adenocarcinomas. Finally, and most importantly, p63(-/-) mice do not develop the prostate. These results indicate that p63 is required for prostate development and support the hypothesis that basal cells represent and/or include prostate stem cells. Furthermore, our results show that p63 immunohistochemistry may be a valuable tool in the differential diagnosis of benign versus malignant prostatic lesions.
Signoretti
S
S
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Waltregny
D
D
Dilks
J
J
Isaac
B
B
Lin
D
D
Garraway
L
L
Yang
A
A
Montironi
R
R
McKeon
F
F
Loda
M
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015415:Biomarkers; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011467:Prostate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D015415:Biomarkers; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins