Regulation of p63 expression in primary and immortalized nasopharyngeal epithelial cells. 2008

Y L Yip, and S W Tsao
Cancer Biology Laboratory, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, P.R. China.

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.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009303 Nasopharyngeal Neoplasms Tumors or cancer of the NASOPHARYNX. Cancer of Nasopharynx,Nasopharyngeal Cancer,Cancer of the Nasopharynx,Nasopharynx Cancer,Nasopharynx Neoplasms,Neoplasms, Nasopharyngeal,Cancer, Nasopharyngeal,Cancer, Nasopharynx,Cancers, Nasopharyngeal,Cancers, Nasopharynx,Nasopharyngeal Cancers,Nasopharyngeal Neoplasm,Nasopharynx Cancers,Nasopharynx Neoplasm,Neoplasm, Nasopharyngeal,Neoplasm, Nasopharynx,Neoplasms, Nasopharynx
D002294 Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed) Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012190 Retroviridae Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES). Leukemogenic Viruses,Leukoviruses,Oncornaviruses,Oncovirinae,Oncoviruses,Oncoviruses, Type C,RNA Tumor Viruses,Retroviruses,Type C Oncoviruses,C Oncovirus, Type,C Oncoviruses, Type,Leukemogenic Virus,Leukovirus,Oncornavirus,Oncovirus,Oncovirus, Type C,RNA Tumor Virus,Retrovirus,Tumor Virus, RNA,Tumor Viruses, RNA,Type C Oncovirus,Virus, Leukemogenic,Virus, RNA Tumor,Viruses, Leukemogenic,Viruses, RNA Tumor
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription

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