title: Heme oxygenase-1 has antitumoral effects in colorectal cancer: involvement of p53.
abstract: 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 an antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity.
authors.affiliation: Laboratorio de Biología del Cáncer - Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico (INIBIBB-CCT-CONICET), Bahía Blanca, Argentina.
authors.forename: Nancy Carolina
authors.initials: NC
authors.lastname: Andrés
authors.affiliation: Laboratorio de Biología del Cáncer - Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico (INIBIBB-CCT-CONICET), Bahía Blanca, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Fermento
authors.affiliation: Laboratorio de Biología del Cáncer - Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico (INIBIBB-CCT-CONICET), Bahía Blanca, Argentina.
authors.forename: Norberto Ariel
authors.initials: NA
authors.lastname: Gandini
authors.affiliation: IACA Laboratorios, Bahía Blanca, Argentina.
authors.forename: Alejandro López
authors.initials: AL
authors.lastname: Romero
authors.affiliation: Servicio de Oncología, Hospital Italiano Regional, Bahía Blanca, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ferro
authors.affiliation: Servicio de Oncología, Hospital Italiano Regional, Bahía Blanca, Argentina.
authors.forename: Lucila Gonzalez
authors.initials: LG
authors.lastname: Donna
authors.affiliation: Laboratorio de Biología del Cáncer - Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico (INIBIBB-CCT-CONICET), Bahía Blanca, Argentina.
authors.forename: Alejandro Carlos
authors.initials: AC
authors.lastname: Curino
authors.affiliation: Laboratorio de Biología del Cáncer - Instituto de Investigaciones Bioquímicas Bahía Blanca, Centro Científico Tecnológico (INIBIBB-CCT-CONICET), Bahía Blanca, Argentina. Electronic address: facchinm@criba.edu.ar.
authors.forename: María Marta
authors.initials: MM
authors.lastname: Facchinetti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000818:Animals; D019540:Area Under Curve; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D012372:ROC Curve; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D016159:Tumor Suppressor Protein p53; D051547:Heme Oxygenase-1
keywords: Colorectal cancer; Heme oxygenase-1; Immunohistochemistry; P53; Survival