P63-driven nuclear accumulation of beta-catenin is not a frequent event in human neoplasms.
deltaN-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 deltaN-p63 may block the phosphorylation of beta-catenin, leading to its nuclear accumulation and triggering beta-catenin-responsive transcription of genes related to proliferation and oncogenic biological behavior. To test this new mechanism, the coexpression of deltaN-p63 and beta-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 deltaN-p63 and beta-catenin monoclonal antibodies. p63 nuclear expression and beta-catenin membranous, cytoplasmic, membranous + cytoplasmic, and nuclear localization were evaluated. deltaN-p63 expression and beta-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 deltaN-p63 and nuclear beta-catenin expression was found for all tumors. At variance with squamous cell carcinoma cell lines, p63-driven nuclear accumulation of beta-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.
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, UK. jorgerf@icr.ac.uk
Jorge S
JS
Reis-Filho
Pete T
PT
Simpson
Laura G
LG
Fulford
Albino
A
Martins
Fernando C
FC
Schmitt
D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D040081:Protein Array Analysis; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D051176:beta Catenin; C077214:L1Hs-encoded protein p40, human