Role of p63 and p73 isoforms on the cell death in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation

Autor: J.M. Pascasio-Acevedo, María A. Rodríguez-Hernández, Sheila Pereira, Jordi Muntané, Miguel Ángel Gómez-Bravo, Elena Navarro-Villarán, Raúl González, Alessandro Rufini, Martina Müller-Schilling, Manuel de la Mata, Trinidad Marchal, Francisco J. Padillo, Ángel J. De la Rosa, M.T. Ferrer-Ríos
Přispěvatelé: Instituto de Salud Carlos III, Junta de Andalucía, European Commission, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), [Gonzalez, Raul] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Inst Biomed Seville IBiS,CSIC, Seville, Spain, [De la Rosa, Angel J.] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Inst Biomed Seville IBiS,CSIC, Seville, Spain, [Rodriguez-Hernandez, Maria A.] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Inst Biomed Seville IBiS,CSIC, Seville, Spain, [Navarro-Villaran, Elena] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Inst Biomed Seville IBiS,CSIC, Seville, Spain, [Pereira, Sheila] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Inst Biomed Seville IBiS,CSIC, Seville, Spain, [Rufini, Alessandro] CRUK Leicester Canc, Dept Canc Studies, Leicester, Leics, England, [Marchal, Trinidad] Hosp Univ Reina Sofia, IMIBIC, Dept Pathol, Cordoba, Spain, [De la Mata, Manuel] Hosp Univ Reina Sofia, IMIBIC, Dept Gastroenterol, Cordoba, Spain, [De la Mata, Manuel] CIBERehd, Madrid, Spain, [Pascasio-Acevedo, Juan M.] CIBERehd, Madrid, Spain, [Ferrer-Rios, Maria T.] CIBERehd, Madrid, Spain, [Gomez-Bravo, Miguel A.] CIBERehd, Madrid, Spain, [Padillo, Francisco J.] CIBERehd, Madrid, Spain, [Muntane, Jordi] CIBERehd, Madrid, Spain, [Mueller-Schilling, Martina] Univ Hosp Heidelberg, Gastroenterol & Hepatol Dept Internal Med 4, Heidelberg, Germany, [Pascasio-Acevedo, Juan M.] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Dept Gastroenterol,CSIC, Seville, Spain, [Ferrer-Rios, Maria T.] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Dept Gastroenterol,CSIC, Seville, Spain, [Gomez-Bravo, Miguel A.] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Dept Gen Surg,CSIC, Seville, Spain, [Padillo, Francisco J.] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Dept Gen Surg,CSIC, Seville, Spain, [Muntane, Jordi] Univ Seville, Hosp Univ Virgen del Rocio, IBiS, Dept Gen Surg,CSIC, Seville, Spain, Institute de Salud Carlos III, Consejeria de Economia, Innovacion, Ciencia y Empleo, Consejeria de Salud, ERDF
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Pathology
Etiology
medicine.medical_treatment
Protein Expression
lcsh:Medicine
Expression
Apoptosis
P53 family
Liver transplantation
Pathology and Laboratory Medicine
Gene
Protein expression
Tumor suppressor proteins
0302 clinical medicine
Receptors
Medicine and Health Sciences
Protein Isoforms
Carcinoma
Hepatocellular
Cell Death
Cell Line
Tumor
Female
Gene Expression Regulation
Neoplastic
Hepatitis B
Hepatitis B virus
Humans
Liver
Liver Neoplasms
Receptors
Death Domain
Transcription Factors
Tumor Protein p73
Tumor Suppressor Proteins
Liver Transplantation
lcsh:Science
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Tumor
Multidisciplinary
Liver Diseases
Oncology
Cell Processes
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Hyperexpression Techniques
Caspase-8
Research Article
medicine.medical_specialty
Orthotopic liver transplantation
Gastroenterology and Hepatology
Research and Analysis Methods
Carcinomas
Cell Line
03 medical and health sciences
Signs and Symptoms
Death Domain
Diagnostic Medicine
Sepsis
Gastrointestinal Tumors
Gene Expression and Vector Techniques
medicine
In patient
Molecular Biology Techniques
Molecular Biology
Differentiated Tumors
neoplasms
Gynecology
Neoplastic
Molecular Biology Assays and Analysis Techniques
business.industry
Flip
Carcinoma
lcsh:R
Proteins
Biology and Life Sciences
Cancers and Neoplasms
Hepatocellular
Cell Biology
Hepatocellular Carcinoma
Binding
medicine.disease
digestive system diseases
030104 developmental biology
Gene Expression Regulation
lcsh:Q
business
Pathway
Zdroj: PLoS ONE
Digital.CSIC. Repositorio Institucional del CSIC
instname
PLoS ONE, Vol 12, Iss 3, p e0174326 (2017)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0174326
Popis: [Background & Aims] Patients 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.
[Methods] 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.
[Results] 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.
[Conclusions] 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.
Instituto de Salud Carlos III (PI13/00021), Consejería de Economía, Innovación, Ciencia y Empleo (CTS-6264) and Consejería de Salud (PI13/00025). CIBERehd founded by Instituto de Salud Carlos III and co-financed by European Development Regional Fund "A way to achieve Europe" ERDF for their support.
Databáze: OpenAIRE
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