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Expression of p53 isoforms in squamous cell carcinoma of the head and neck.
Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Patologi.
Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
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2007 (English)In: Eur J Cancer, ISSN 0959-8049, Vol. 43, no 3, 617-23 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2007. Vol. 43, no 3, 617-23 p.
Keyword [en]
Carcinoma; Squamous Cell/genetics/*metabolism, DNA; Complementary/metabolism, Genes; p53, Head and Neck Neoplasms/genetics/*metabolism, Humans, Immunoblotting/methods, Protein Isoforms, RNA; Messenger/metabolism, RNA; Neoplasm/metabolism, Reverse Transcriptase Polymerase Chain Reaction/methods, Transcription; Genetic, Tumor Suppressor Protein p53/*metabolism
Identifiers
URN: urn:nbn:se:umu:diva-16467DOI: 10.1016/j.ejca.2006.10.019PubMedID: 17215121OAI: oai:DiVA.org:umu-16467DiVA: diva2:156140
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2009-03-06Bibliographically approved
In thesis
1. p63 and potential p63 targets in squamous cell carcinoma of the head and neck
Open this publication in new window or tab >>p63 and potential p63 targets in squamous cell carcinoma of the head and neck
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Squamous cell carcinoma of the head and neck (SCCHN), the 6th most common cancer worldwide, has a low 5-year survival. Disease as well as treatment often causes patients severe functional and aesthetic problems. In order to improve treatment and diagnosis at earlier stages of tumour development it is important to learn more about the molecular mechanisms behind the disease. p63, an important regulator of epithelial formation, has been suggested to play a role in the development of SCCHN. Six different isoforms of p63 have been found and shown to have various functions. The aim of the studies in this thesis was to learn more about the role of p63 and proteins connected to p63 in SCCHN.

Expression of p63, Cox-2, EGFR, beta-catenin, PP2A and p53 isoforms was mapped in tumours and normal tumour adjacent tissue from patients with SCCHN using western blot or RT-PCR. Results showed no significant difference between tumours and normal tumour adjacent tissue concerning expression of EGFR and beta-catenin. Cox-2 and PP2A showed significantly higher expression in tumours while p63 was more expressed in normal tumour adjacent tissue. However, expression of all these proteins in normal tumour adjacent tissue differed from tissue from disease-free non-smoking individuals. Smoking in itself did not affect expression of these proteins. The p53 isoforms p53, p53beta, p53gamma, ∆133p53, ∆133p53beta and ∆133p53gamma were expressed at RNA level in samples both from tumours and normal tumour adjacent tissue, though most of them at fairly low levels.

The functional properties of the different p63 isoforms have not been fully mapped. By establishing stable cell lines over-expressing the different p63 isoforms we investigated their specific effect on tumour cells from SCCHN. Only the ∆Np63 isoforms could be stably over-expressed, whereas no clones over-expressing TAp63 could be established. Using microarray technique, cell lines stably expressing the ∆Np63 isoforms were studied and CD44, Keratins 4, 6, 14, 19 and Cox-2 were found to be regulated by p63.

In conclusion, the present project adds new data to the field of p63 and SCCHN. For example, we have shown that clinically normal tumour adjacent tissue is altered compared to normal oral mucosa in non tumour patients, and that smoking does not change expression of p63, Cox-2, EGFR, beta-catenin or PP2A in oral mucosa. Novel p53 isoforms are expressed in SCCHN, and even though levels are very low they should not be overlooked. Furthermore, CD44, keratins 4, 6, 14, 19 and Cox-2 were identified as p63 targets in SCCHN.

Place, publisher, year, edition, pages
Umeå: Medicinsk biovetenskap, 2008. 60 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1148
Keyword
SCCHN, p63, Cox-2, EGFR, β-catenin, PP2A, p53
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-1522 (URN)978-91-7264-473-1 (ISBN)
Public defence
2008-02-22, Betula, 6M, Umeå Universitet, SE-90185, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2008-02-04 Created: 2008-02-04 Last updated: 2009-03-13Bibliographically approved

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