Academic Journal

Nrf2 Mutation/Activation Is Dispensable for the Development of Chemically Induced Mouse HCCSummary

التفاصيل البيبلوغرافية
العنوان: Nrf2 Mutation/Activation Is Dispensable for the Development of Chemically Induced Mouse HCCSummary
المؤلفون: Sandra Mattu, Patrizia Zavattari, Marta Anna Kowalik, Marina Serra, Pia Sulas, Rajesh Pal, Elisabetta Puliga, Salvatore Sutti, Beatrice Foglia, Maurizio Parola, Emanuele Albano, Silvia Giordano, Andrea Perra, Amedeo Columbano
المصدر: Cellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 1, Pp 113-127 (2022)
بيانات النشر: Elsevier, 2022.
سنة النشر: 2022
المجموعة: LCC:Diseases of the digestive system. Gastroenterology
مصطلحات موضوعية: Nrf2, Ctnnb1, Gene Mutation, Metabolic Reprogramming, HCC, Diseases of the digestive system. Gastroenterology, RC799-869
الوصف: Background & Aims: Activation of the kelch-like ECH-associated protein 1 (Keap1)–nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway has been associated with metabolic reprogramming in many tumors, including hepatocellular carcinoma (HCC). However, the contribution of Nrf2 mutations in this process remains elusive. Here, we investigated the occurrence of Nrf2 mutations in distinct models of mouse hepatocarcinogenesis. Methods: HCCs were generated by experimental protocols consisting of the following: (1) a single dose of diethylnitrosamine (DEN), followed by repeated treatments with the nuclear-receptor agonist 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene; (2) repeated treatments with 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene alone; (3) a single dose of DEN followed by exposure to a choline-deficient L-amino acid–defined diet; and (4) a single dose of DEN with no further treatment. All of these protocols led to HCC development within 28–42 weeks. Activation of the Keap1-Nrf2 pathway was investigated by analyzing the presence of Nrf2 gene mutations, and the expression of Nrf2 target genes. Metabolic reprogramming was assessed by evaluating the expression of genes involved in glycolysis, the pentose phosphate pathway, and glutaminolysis. Results: No Nrf2 mutations were found in any of the models of hepatocarcinogenesis analyzed. Intriguingly, despite the described cooperation between β-catenin and the Nrf2 pathway, we found no evidence of Nrf2 activation in both early dysplastic nodules and HCCs, characterized by the presence of up to 80%–90% β-catenin mutations. No HCC metabolic reprogramming was observed either. Conclusions: These results show that, unlike rat hepatocarcinogenesis, Nrf2 mutations do not occur in 4 distinct models of chemically induced mouse HCC. Interestingly, in the same models, metabolic reprogramming also was minimal or absent, supporting the concept that Nrf2 activation is critical for the switch from oxidative to glycolytic metabolism.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-345X
Relation: http://www.sciencedirect.com/science/article/pii/S2352345X21001788; https://doaj.org/toc/2352-345X
DOI: 10.1016/j.jcmgh.2021.08.011
URL الوصول: https://doaj.org/article/a287ac6f649144fb9e8b07c7fac86783
رقم الانضمام: edsdoj.287ac6f649144fb9e8b07c7fac86783
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2352345X
DOI:10.1016/j.jcmgh.2021.08.011