Gonzalez, RaulDe la Rosa, Angel JRufini, AlessandroRodriguez-Hernandez, Maria ANavarro-Villaran, ElenaMarchal, TrinidadPereira, SheilaDe la Mata, ManuelMüller-Schilling, MartinaPascasio-Acevedo, Juan MFerrer-Rios, Maria TGomez-Bravo, Miguel APadillo, Francisco JMuntane, Jordi2023-01-252023-01-252017-03-07González R, De la Rosa ÁJ, Rufini A, Rodríguez-Hernández MA, Navarro-Villarán E, Marchal T, et al. Role of p63 and p73 isoforms on the cell death in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation. PLoS One. 2017 Mar 28;12(3):e0174326http://hdl.handle.net/10668/11017Patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT) have a variable 5-year survival rate limited mostly by tumor recurrence. The etiology, age, sex, alcohol, Child-Pugh, and the immunesuppressor have been associated with tumour recurrence. The expression of ΔNp73 is related to the reduced survival of patients with HCC. The study evaluated the expression of p63 and p73 isoforms and cell death receptors, and their relation to tumour recurrence and survival. The results were in vitro validated in HCC cell lines. HCC sections from patients submitted to OLT were used. The in vitro study was done in differentiated hepatitis B virus (HBV)-expressing Hep3B and control HepG2 cells. The expression of cell death receptors and cFLIPS/L, caspase-8 and -3 activities, and cell proliferation were determined in control and p63 and p73 overexpressing HCC cells. The reduced tumor expression of cell death receptors and TAp63 and TAp73, and increased ΔNp63 and ΔNp73 expression were associated with tumor recurrence and reduced survival. The in vitro study demonstrated that HBV-expressing Hep3B vs HepG2 cells showed reduced expression of p63 and p73, cell death receptors and caspase activation, and increased cFLIPL/cFLIPS ratio. The overexpression of TAp63 and TAp73 exerted a more potent pro-apoptotic and anti-proliferative effects in Hep3B than HepG2-transfected cells which was related to cFLIPL upregulation. The reduction of TAp63 and TAp73 isoforms, rather than alteration of ΔN isoform expression, exerted a significant functional repercussion on cell death and proliferation in HBV-expressing HepB cells.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Protein IsoformsReceptors, Death DomainTranscription FactorsTumor Protein p73Tumor Suppressor ProteinsCarcinoma, HepatocellularCell DeathCell Line, TumorFemaleGene Expression Regulation, NeoplasticHepatitis BHepatitis B virusHumansLiverLiver NeoplasmsLiver TransplantationMaleresearch article28350813open accessCarcinoma hepatocelularHígadoLínea celular tumoralMuerte celularNeoplasias hepáticasRegulación neoplásica de la expresión génicaTrasplante de hígadoVirus de la Hepatitis B10.1371/journal.pone.01743261932-6203PMC5369777https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0174326&type=printablehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369777/pdf