Involvement of N-terminally truncated variants of p73, deltaTAp73, in head and neck squamous cell cancer: a comparison with p53 mutations.

p73, a p53-related gene, encodes two classes of isoforms with opposing functions: (1) a full-length transactivation-competent p73 protein (TAp73) with tumour suppressor activity; and (2) a group of NH2-terminally truncated, transactivation-deficient p73 proteins, deltaEx2p73, deltaEx2-3p73, deltaNp73 and deltaN'p73 (collectively named deltaTAp73) with oncogenic activity. In this study, for the first time, we analyse the deregulations of TAp73 and deltaTAp73 in head and neck squamous cell cancer (HNSCC) and compare them to p53 status. We found that all the p73 isoforms in HNSCC tissue were upregulated with respect to those in normal adjacent tissue.

P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer cells.

p53-Related genes, p73 and p63, encode 2 classes of proteins, TA-p73/p63 and DeltaN-p73/p63. TA-p73/p63 demonstrate p53-like properties including gene transactivation and cell death promotion, whereas DeltaN-p73/p63 lack these p53-like functions. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work.

Expression of p53-family members and associated target molecules in breast cancer cell lines in response to vincristine treatment.

As the antimitotic agent vincristine (VCR) has been reported to induce a weak p53 response in some studies, we hypothesised that p73 and p63, the recently described p53 homologues, may replace p53 in triggering apoptosis or cell cycle arrest effectors in VCR-treated cell lines. To address this issue, we measured p53, p73 and p63 mRNA and protein levels in two VCR-treated breast cancer cell lines, one p53-proficient (MCF7) and the other p53-deficient (MDA-MB157). We found an increase of p53 mRNA and protein levels in VCR-treated MCF7 cells, while, as expected, no p53 protein was detected in VCR-treated MDA-MB157 cells.

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

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.

No evidence of somatic FGFR3 mutation in various types of carcinoma.

Germline specific point mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) are associated with autosomal dominant human skeletal dysplasia and craniosynostosis syndromes. Mutations identical to the germinal activating mutations found in severe skeletal dysplasias have been identified in certain types of cancer: at low frequency in multiple myeloma and cervix carcinoma and at high frequency in bladder carcinoma. We analysed, by SSCP and sequencing, the prevalence of FGFR3 mutations in 116 primary tumours of various types (upper aerodigestive tract, oesophagus, stomach, lung and skin).