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 |
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| 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 |
| 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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