Home LiteratureArticle Details
PMID: 11106548 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

p63 is a prostate basal cell marker and is required for prostate development.

The American journal of pathology ·Vol. 157 ·No. 6 ·2000-12-00 ·Pages 1769-75

Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M

Abstract

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.

MeSH Terms
Adenocarcinoma/metabolism,pathology Animals Biomarkers Cell Nucleus/metabolism Cells, Cultured DNA-Binding Proteins Epithelial Cells/metabolism Genes, Tumor Suppressor Humans Male Membrane Proteins Mice Mice, Inbred Strains Neoplasm Invasiveness Phosphoproteins/metabolism,physiology Prostate/cytology,growth & development,metabolism Prostatic Intraepithelial Neoplasia/metabolism,pathology Prostatic Neoplasms/metabolism,pathology Protein Isoforms/metabolism Reference Values Trans-Activators Transcription Factors Tumor Suppressor Proteins
Chemicals
Biomarkers CKAP4 protein, human DNA-Binding Proteins Membrane Proteins Phosphoproteins Protein Isoforms TP63 protein, human Trans-Activators Transcription Factors Trp63 protein, mouse Tumor Suppressor Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Signoretti S
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Waltregny D
Dilks J
Isaac B
Lin D
Garraway L
Yang A
Montironi R
McKeon F
Loda M
References (27)
27 references, click to expand
  1. Keratin expression: a measure of phenotypic modulation of human prostatic epithelial cells by growth inhibitory factors.
    Cell Tissue Res. 1994 Jul;277(1):11-8 PMID: 7519968
  2. Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers.
    Am J Pathol. 1993 Aug;143(2):390-400 PMID: 7688182
  3. p53-mediated transcriptional activity increases in differentiating epidermal keratinocytes in association with decreased p53 protein.
    Oncogene. 1995 Jun 15;10(12):2271-9 PMID: 7784075
  4. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27.
    Science. 1995 Aug 4;269(5224):682-5 PMID: 7624798
  5. Cell-cell interaction in prostate gene regulation and cytodifferentiation.
    Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10705-10 PMID: 9380699
  6. Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1735-40 PMID: 9465086
  7. A new human p53 homologue.
    Nat Med. 1998 Jul;4(7):747-8 PMID: 9662346
  8. Cloning and functional analysis of human p51, which structurally and functionally resembles p53.
    Nat Med. 1998 Jul;4(7):839-43 PMID: 9662378
  9. p53 protein is activated during muscle differentiation and participates with MyoD in the transcription of muscle creatine kinase gene.
    Oncogene. 1998 Jul 23;17(3):347-56 PMID: 9690516
  10. A second p53-related protein, p73L, with high homology to p73.
    Biochem Biophys Res Commun. 1998 Jul 30;248(3):603-7 PMID: 9703973
  11. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.
    Mol Cell. 1998 Sep;2(3):305-16 PMID: 9774969
  12. Basal cells are progenitors of luminal cells in primary cultures of differentiating human prostatic epithelium.
    Prostate. 1998 Nov 1;37(3):149-60 PMID: 9792132
  13. Real-time quantitative RT-PCR after laser-assisted cell picking.
    Nat Med. 1998 Nov;4(11):1329-33 PMID: 9809560
  14. Roles for Nkx3.1 in prostate development and cancer.
    Genes Dev. 1999 Apr 15;13(8):966-77 PMID: 10215624
  15. p63 is a p53 homologue required for limb and epidermal morphogenesis.
    Nature. 1999 Apr 22;398(6729):708-13 PMID: 10227293
  16. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development.
    Nature. 1999 Apr 22;398(6729):714-8 PMID: 10227294
  17. Association of p63 with proliferative potential in normal and neoplastic human keratinocytes.
    J Invest Dermatol. 1999 Dec;113(6):1099-105 PMID: 10594758
  18. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.
    Oncogene. 2000 Mar 2;19(10):1288-96 PMID: 10713670
  19. Cytokeratin characterization of human prostatic carcinoma and its derived cell lines.
    Cancer Res. 1987 Jan 1;47(1):281-6 PMID: 2431765
  20. The endocrinology and developmental biology of the prostate.
    Endocr Rev. 1987 Aug;8(3):338-62 PMID: 3308446
  21. Response of glandular versus basal rat ventral prostatic epithelial cells to androgen withdrawal and replacement.
    Prostate. 1987;11(3):229-42 PMID: 3684783
  22. Cell proliferation studies in the rat prostate: II. The effects of castration and androgen-induced regeneration upon basal and secretory cell proliferation.
    Prostate. 1987;11(4):339-51 PMID: 3684785
  23. Differential expression of keratins in the basal and luminal compartments of rat prostatic epithelium during degeneration and regeneration.
    Prostate. 1988;13(1):25-38 PMID: 2458583
  24. Leukemia and the disruption of normal hematopoiesis.
    Cell. 1991 Jan 25;64(2):337-50 PMID: 1988151
  25. Studies on the proliferation, secretory activities, and epidermal growth factor receptor expression in benign prostatic hyperplasia explant cultures.
    Prostate. 1992;20(2):133-49 PMID: 1372429
  26. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer.
    Cancer Res. 1992 Dec 15;52(24):6940-4 PMID: 1458483
  27. c-met proto-oncogene expression in benign and malignant human prostate tissues.
    J Urol. 1995 Jul;154(1):293-8 PMID: 7539865
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)64814-6
Published
2000-12-00
Pages
1769-75
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1885786
Subset
IM
Grants
NCI NIH HHS · CA 81755-03 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)64814-6 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2