Regulation of p63 expression in primary and immortalized nasopharyngeal epithelial cells.
Mutation of the p53 gene is a common event in human cancer. Interestingly, p53 mutation is uncommon in nasopharyngeal carcinoma (NPC). The DeltaNp63 has been postulated to have a dominant-negative effect on the function of the p53 gene and may play a role in the pathogenesis of nasopharyngeal carcinoma. Immortalization is a common property of cancer cells and is believed to be an early event in carcinogenesis. At present, the relationship between DeltaNp63 and immortalization is poorly understood. In this study, we defined the expression profile of p63 and its various isoforms in primary and immortalized nasopharyngeal epithelial cells. Also, we elucidated some events regulating the expression of p63. Elevated expression of p63 was generally detected in both primary and immortalized nasopharyngeal epithelial cells at their proliferation stage and the predominant isoform of p63 expressed was DeltaNp63alpha. p63 expression was suppressed upon cellular senescence of primary nasopharyngeal epithelial cells and induction of terminal differentiation in immortalized nasopharyngeal epithelial cells. Expression of DeltaNp63 alone was able to drive clonal proliferation in primary nasopharyngeal cells in culture while downregulation of DeltaNp63 induced cellular apoptosis. All these results support a role of DeltaNp63 in proliferation and immortalization which facilitates pathogenesis of nasopharyngeal carcinoma. TGFbeta and retinoic acid downregulated the expression of p63 in immortalized nasopharyngeal epithelial cells and may play a role in regulating differentiation in squamous epithelial cells with potential applications in prevention and treatment of nasopharyngeal carcinoma.
Yip
Y L
YL
Cancer Biology Laboratory, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China.
Tsao
S W
SW
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence; D018076:DNA, Complementary / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D012313:RNA / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018076:DNA, Complementary; C508960:TGFB1 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D012313:RNA