p63-driven Nuclear Accumulation of β-Catenin is Not a Frequent Event in Human Neoplasms

• Published in: Pathology, research and practice Vol. 199; no. 12; pp. 785 - 793
• Main Authors: Reis-Filho, Jorge S., Simpson, Pete T., Fulford, Laura G., Martins, Albino, Schmitt, Fernando C.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 2003
• Subjects: beta Catenin; Cell Nucleus - metabolism; Cell Nucleus - pathology; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - metabolism; Female; Humans; Immunoenzyme Techniques; Male; Neoplasms - metabolism; Neoplasms - pathology; Protein Array Analysis; Trans-Activators - metabolism
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1078/0344-0338-00497

ΔN-p63 isoforms may act as oncogenes owing to their ability to bind to p53-reporter genes without inciting their transcription, thus blocking the p53-driven cell cycle arrest and apoptosis. A novel mechanism linking p63 and Wnt pathways has recently been proposed. Briefly in vitro studies using squamous cell carcinoma cell lines have suggested that ΔN-p63 may block the phosphorylation of β-catenin, leading to its nuclear accumulation and triggering β-catenin-responsive transcription of genes related to proliferation and oncogenic biological behavior. To test this new mechanism, the co-expression of ΔN-p63 and β-catenin was evaluated in a large cohort of human neoplasms. Two serial sections of TARP-4 multi-tumor tissue microarray, composed of 51 normal tissue cores and 400 human neoplasms [breast (n=75), colon (n=75), lung (n=75), prostate (n=75) and ovary (n=50) neoplasms, melanoma (n=25), and glioblastoma (n=25)] were subjected to immunohistochemistry with ΔN-p63 and β-catenin monoclonal antibodies. p63 nuclear expression and β-catenin membranous, cytoplasmic, membranous+cytoplasmic, and nuclear localization were evaluated. ΔN-p63 expression and β-catenin nuclear localization were found in 92.6% and 0% of squamous cell carcinomas, 8.9% and 0% of breast carcinomas, 13.8% and 0% of lung adenocarcinomas, 1.4% and 23.2% of colon adenocarcinomas, 0% and 4.8% of prostate adenocarcinomas, 11.1% and 5% of ovary carcinomas, 9.0% and 9.1% of malignant melanomas, and 12.5% and 40.0% of glioblastomas, respectively. No statistically significant association between ΔN-p63 and nuclear β-catenin expression was found for all tumors. At variance with squamous cell carcinoma cell lines, p63-driven nuclear accumulation of β-catenin is an unusual phenomenon in human neoplasms. Caution should be exercised when translating the results of studies performed on cell lines to human neoplasms.