Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
| Autor: | María Eugenia Fermento, Maria Marta Facchinetti, Lucila Gonzalez Donna, Norberto Ariel Gandini, Alejandro Ferro, Alejandro Carlos Curino, Alejandro López Romero, Nancy Carolina Andrés |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Cell cycle checkpoint CIENCIAS MÉDICAS Y DE LA SALUD Colorectal cancer Clinical Biochemistry Blotting Western Kaplan-Meier Estimate Biology Adenocarcinoma Bioinformatics Transfection Pathology and Forensic Medicine Cyclin D1 Cell Line Tumor medicine Animals Humans Viability assay IMMUNOHISTOCHEMISTRY Rats Wistar Molecular Biology Protein kinase B COLORECTAL CANCER P53 Patología medicine.disease Flow Cytometry Immunohistochemistry Rats Heme oxygenase Disease Models Animal Medicina Básica ROC Curve Tumor progression Apoptosis Area Under Curve Cancer research SURVIVAL Female Tumor Suppressor Protein p53 HEME OXYGENASE-1 Colorectal Neoplasms Heme Oxygenase-1 |
| Popis: | The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate and antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity. Fil: Andrés, Nancy Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Bahia Blanca. Instituto de Investigaciones Bioquimicas Bahia Blanca (i); Argentina Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Bahia Blanca. Instituto de Investigaciones Bioquimicas Bahia Blanca (i); Argentina Fil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Bahia Blanca. Instituto de Investigaciones Bioquimicas Bahia Blanca (i); Argentina Fil: Lopez Romero, Alejandro. IACA Laboratorios; Argentina Fil: Ferro, Alejandro. Hospital Italiano Regional del Sur. Servicio de Oncología; Argentina Fil: Gonzalez Donna, Lucila. Hospital Italiano Regional del Sur. Servicio de Oncología; Argentina Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Bahia Blanca. Instituto de Investigaciones Bioquimicas Bahia Blanca (i); Argentina Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Bahia Blanca. Instituto de Investigaciones Bioquimicas Bahia Blanca (i); Argentina |
| Databáze: | OpenAIRE |
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