P73 expression in basal layers of head and neck squamous epithelium: a role in differentiation and carcinogenesis in concert with p53 and p63?

Autor: Marie‐Luce Le Bihan, Muriel Vayssade, Jean-Charles Ahomadegbe, Daniel Caput, Jacques Bosq, Laetitia Faridoni-Laurens, Mourad Kaghad, Jean Bénard, François Janot
Rok vydání: 2001
Předmět:
Heterozygote
Cancer Research
Pathology
medicine.medical_specialty
Morphogenesis
Down-Regulation
Loss of Heterozygosity
Biology
medicine.disease_cause
Loss of heterozygosity
Basal (phylogenetics)
Genetics
medicine
Humans
Genes
Tumor Suppressor
RNA
Messenger
skin and connective tissue diseases
neoplasms
Molecular Biology
Alleles
Hypopharyngeal Neoplasms
Models
Genetic
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Proteins
Membrane Proteins
Nuclear Proteins
Cell Differentiation
Epithelial Cells
Tumor Protein p73
Phosphoproteins
Immunohistochemistry
Epithelium
Staining
DNA-Binding Proteins
medicine.anatomical_structure
Head and Neck Neoplasms
Mutation
Immunology
Carcinoma
Squamous Cell
Trans-Activators
Tumor Suppressor Protein p53
Carcinogenesis
Immunostaining
Transcription Factors
Zdroj: Oncogene. 20:5302-5312
ISSN: 1476-5594
0950-9232
Popis: P73, a p53-homologue gene, has been studied for its possible role in head and neck squamous epithelium (HNSE) differentiation and carcinogenesis. P73 RNA and protein were analysed in 50 biopsies, including well- and moderately-differentiated carcinomas, and 21 matched normal adjacent tissues. P73 immunohistochemical analyses revealed intense p73 nuclear staining in basal and parabasal cells of normal squamous epithelium, in contrast with complete absence of staining in the more superficial cell layers. Moderately-differentiated carcinomas demonstrated homogeneous and diffuse staining in all tumour cells, while only basal cells were stained in well-differentiated carcinomas as in normal tissue. No correlation was observed between p73 and p53 protein expression. Immunostaining for p63, another p53-related protein previously described as being involved in HNSE morphogenesis and overexpressed in head and neck squamous cell carcinomas (HNSCC), was found to be similar to p73 labelling in carcinomas, but spread to the more differentiated layers in normal epithelium. Biallelic expression of p73 was found in tumours as well as in matched normal tissues. Comparison of p73 transcript levels between tumours and normal tissues showed decreased mRNA expression in 5/17 (30%) tumours independently of the differentiation status. Mutation and loss of heterozygosity analyses of the p73 gene revealed wild type status and no deletion. Our results strongly suggest that: (i) p73 is associated with homeostasis and control of differentiation of head and neck squamous epithelium probably in concert with p53 and p63; (ii) down-regulation of p73 expression could participate in HNSE carcinogenesis.
Databáze: OpenAIRE
Externí odkaz: