Differential expression of p63 isoforms in normal tissues and neoplastic cells

The p63 gene encodes at least six different proteins with homology to the tumour suppressor protein p53 and the related p53 family member p73. So far, there have been limited data concerning the expression patterns of individual p63 proteins, due to a lack of reagents that distinguish between the di...

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Bibliographic Details
Published in:The Journal of pathology 2002-12, Vol.198 (4), p.417-427
Main Authors: Nylander, Karin, Vojtesek, Borek, Nenutil, Rudolf, Lindgren, Britta, Roos, Göran, Zhanxiang, Wang, Sjöström, Björn, Dahlqvist, Åke, Coates, Philip J
Format: Article
Language:English
Subjects:
adenocarcinoma
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Cell Culture Techniques
DNA-Binding Proteins
Epithelium - metabolism
Female
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
General aspects
Genes, Tumor Suppressor
Humans
Immune Sera - immunology
lymphoma
Lymphoma - genetics
Lymphoma - metabolism
Male
Medical sciences
Membrane Proteins
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Neoplasms - genetics
Neoplasms - metabolism
p63
Phosphoproteins - genetics
Phosphoproteins - metabolism
Protein Isoforms - genetics
Protein Isoforms - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Neoplasm - genetics
squamous cell carcinoma
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription Factors
Tumor Cells, Cultured
Tumor Suppressor Proteins
Tumors
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Summary:The p63 gene encodes at least six different proteins with homology to the tumour suppressor protein p53 and the related p53 family member p73. So far, there have been limited data concerning the expression patterns of individual p63 proteins, due to a lack of reagents that distinguish between the different isoforms. Three antibodies have been produced specifically directed against the two N‐terminal isoforms (TAp63 and ΔNp63) and the C‐terminal region of the p63α proteins. TAp63 proteins are located suprabasally in stratified epithelia compared with the N‐terminal truncated forms, which are more abundantly expressed in the basal cell layer, indicating a switch in expression of p63 isoforms during normal cellular differentiation. Analysis of squamous cell carcinomas shows ΔNp63α to be the most widely expressed isoform, compatible with a role for this protein in promoting neoplastic cell growth in these tissues. ΔNp63 protein expression is also restricted to basal cells in breast and prostate, whilst TAp63 isoforms are more widely expressed in these tissues as well as in tumours at these sites. TAp63, but not ΔNp63 or p63α, is detected in normal colon and in colon carcinoma. TAp63 proteins are also expressed in the nuclei of a sub‐population of lymphoid cells and in most malignant lymphomas, whereas ΔNp63 proteins are not expressed. Taken together, a hitherto unrecognized regulation of p63 isoform expression in vivo has been uncovered, with different p63 proteins expressed during differentiation and in different cell types. The data indicate roles for specific p63 isoforms not only in maintaining epithelial stem cell populations, but also in cellular differentiation and neoplasia. Copyright © 2002 John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.1231