Health & Environmental Research Online (HERO)


Print Feedback Export to File
454635 
Journal Article 
Delta Np63 isoforms differentially regulate gene expression in squamous cell carcinoma: identification of Cox-2 as a novel p63 target 
Boldrup, L; Coates, PJ; Gu, XL; Nylander, K 
2009 
Yes 
Journal of Pathology
ISSN: 0022-3417
EISSN: 1096-9896 
218 
4 
428-436 
English 
The p53 homologue p63 produces six different isoforms that are important in development of epithelial tissues and squamous cell carcinoma of the head and neck (SCCHN). In SCCHN, the expression of p63 isoforms is highly complex, with over-expression of Delta Np63 and p63 beta isoforms in many tumours. To date, little is known about the functions of different Delta Np63 isoforms and elucidating the distinctive properties of Delta Np63 isoforms will help to clarify how they influence tumour biology. By gene expression profiling of SCCHN cells over-expressing the Delta Np63 isoforms we identified different effects of the three isoforms, with Delta Np63 beta being more effective at gene induction than Delta Np63 alpha and Delta Np63 gamma, whereas Delta Np63 gamma was most effective at repressing gene expression. Thus, tumours expressing even low levels of Delta Np63 beta or Delta Np63 gamma may, have distinct clinicopathological characteristics important for metastasis and therapeutic response. Induction of cyclooxygenase-2 (Cox-2) was shown by each isoform and data were confirmed by independent quantitative RT-PCR and western blotting. No direct binding of Delta Np63 to the Cox-2 promoter could be seen, neither could any evidence for Cox-2 induction as a consequence of activated NF-kappa B pathway responses be found. As Cox-2 is known to inhibit radiotherapy responses in SCCHN patients, data indicate an additional mechanism through which Delta Np63 acts to promote cell survival and influence therapeutic response of SCCHN. MIAME-compliant data have been deposited in the MIAME Express database (Accession No. E-MEXP-1842). Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 
p63; Cox-2; SCCHN; microarray; cell lines; growth-factor receptor; factor-kappa-b; p53 homolog; smokeless tobacco; induced apoptosis; mutations lead; cancer-cells; cyclooxygenase-2; head; neck