Browsing by Subject "p73"

Now showing 1 - 3 of 3
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    Expression and prognostic significance of YAP, TAZ, TEAD4 and p73 in human laryngeal cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Tsinias, Georgios; Nikou, Sofia; Mastronikolis, Nicholas; Bravou, Vasiliki; Papadaki, Helen
    Objectives. The Hippo signaling pathway plays a critical role in organ size control and tissue homeostasis and its perturbation is associated with tumorigenesis. YAP (Yes associated protein) and TAZ (transcriptional co-activator with PDZ- binding motif) are the major nuclear effectors of the Hippo pathway interacting with TEADs (TEA domain) and p73 transcriptional factors to regulate gene expression. Altered expression of the above proteins promotes tumor initiation, progression and metastasis in a variety of cancer types. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Methods. Protein expression of YAP, TAZ, TEAD4 and p73 was examined by immunohistochemistry in 121 human laryngeal squamous cell carcinomas. Correlations with clinicopathological data and survival were evaluated. Results. All proteins were overexpressed in human laryngeal carcinomas compared to non-neoplastic adjacent epithelium. High expression of YAP, TAZ, TEAD4 and p73 correlated significantly with high grade, advanced stage, supraglottic location of tumor, nodal metastases and recurrence. Furthermore, high expression of all proteins was significantly associated with poor overall and disease- free survival. p73 expression proved to be an independent predictive factor of survival and YAP expression proved to be an independent predictive factor of disease recurrence. Conclusions. Deregulation of the expression of the Hippo pathway proteins is implicated in human laryngeal carcinogenesis and YAP and p73 have prognostic significance in the outcome of the disease
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    The diverse oncogenic and tumour suppressor roles of p63 and p73 in cancer: a review by cancer site
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Orzol, Paulina; Holcakova, Jitka; Nekulova, Marta; Nenutil, Rudolf; Vojtesek, Borivoj; Coates, Philip J.
    p63 and p73, the two other members of the p53 family, were identified almost 15 years ago. Here, we review their potential use for diagnosis, prognosis and prediction of response to therapy in various cancers. The two genes show distinct expression patterns in both normal and cancer tissues and each gene gives rise to multiple protein isoforms with different activities, including those with tumour-suppressor or oncogenic effects. Despite such complexity, some common themes emerge; p63 is commonly overexpressed as the ΔNp63 isoform and sometimes associated with TP63 amplification, whereas p73 is often reduced (by methylation or gene loss), or there is an increase in the ratio of ΔNp73 to TAp73. These generalisations do not apply universally; TAp63 is overexpressed in haematological malignancies, TP63 mis-sense mutations have been reported in squamous cancers and TP63 translocations occur in lymphomas and some lung adenocarcinomas. There are associations with disease prognosis and response to specific therapies in individual cancer types for both p63 and p73, making their analysis of clinical relevance. We also discuss their utility for aiding in differential diagnosis, which has been demonstrated for p63, but not yet for p73. Throughout, we highlight the discrepant nature of many studies due to the variable methodologies employed, the lack of systematic evaluation of isoforms and the problems of poor antibody characterization and crossreactions within the p63/p73 family. Finally, we emphasize the value of recently developed isoformspecific reagents that have clear advantages for the study of p63 and p73 experimentally and clinically.
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    The expression of p73 in the organum vasculosum of the lamina terminalis and choroid plexus of spontaneously hypertensive rats
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Carmona-Calero, E.M.; Castañeyra-Ruiz, L.; González-Toledo, J.M.; Paz-Carmona, H. de; Brage, C.; Castañeyra-Ruiz, A.; Rancel-Torres, M.N.; González-Marrero, I.; Castañeyra-Perdomo, A.
    The p73 proteins are present in different kinds of cells of the central nervous system, such as the choroid plexus, circumventricular structures and neuroepithelium. It has been reported that spontaneously hypertensive rats show ventricular dilation, changes in cerebrospinal fluid proteins and variations in the circumventricular structures such as the organum vasculosum of the lamina terminalis and the choroid plexus, which are altered in ventricular dilation. The aim of the present work is to study p73 expression in the organum vasculosum of the lamina terminalis and the choroid plexus and its variations in high blood pressure. Brains from control Wistar-Kyoto rats and spontaneously hypertensive rats were used. The organum vasculosum of the lamina terminalis and the choroid plexus were processed by immunohistochemistry and western blot with anti-TAp73. We found weaker markings in the organum vasculosum of the lamina terminalis and stronger markings in the choroid plexus of the hypertensive than the control rats. Therefore, hypertension in the spontaneously hypertensive rats produces alterations in choroid plexus protein p73 expression that is similar to that described for other circumventricular organs, but it is different in the organum vasculosum of the lamina terminalis. We can conclude that the functional balance between p73, organum vasculosum of the lamina terminalis and choroid plexus, which is probably necessary to maintain the normal functioning of these structures, is altered by the hypertension found in these rats.