Unfolded protein response during the progression of colorectal carcinogenesis

• Published in: Acta Cirúrgica Brasileira 2025-01, Vol.40
• Main Authors: Augusto Sobrinho, Cesar, Almeida, Alexandre Moreira de, Grigolo, Maytana Roberta Taschin, Selzler, Michele, Abreu, Antônio Carlos de, Fagundes, Letícia Silva, Martins, Almir Souza, Palhares, Durval Batista, Ramalho, Rondon Tosta
• Format: Article
• Language: English
• Subjects: Colorectal Neoplasms; Endoplasmic Reticulum Stress; Original; Unfolded Protein Response
• ISSN: 0102-8650; 1678-2674
• DOI: 10.1590/acb400725

ABSTRACT Purpose: To evaluate the molecular evolution of endoplasmic reticulum (ER) stress during colorectal cancer carcinogenesis. Methods: Fifty-six hairless mice were divided into two groups: control (no intervention); and carcinogenesis (treated with two doses of azoxymethane at 10 mg/kg during the third and the fourth week and dextran sodium sulfate at 2.5% for seven days in the second, fifth, and eighth week). Euthanasia occurred at the fifth, 10th, 15th, and 20th week. Colons were collected, and gene expression of ER stress markers (IRE1-α, PERK, ATF6, and CHOP) was assessed via real-time quantitative polymerase chain reaction. Results: ERN1 expression was significantly higher than the control at the 10th week (1.39 ± 0.16, p 0.05) and the 20th week (1.15 ± 0.04, p 0.01). ATF6 also showed elevated expression, significantly different at the 10th week (1.71 ± 0.29, p 0.05) and the 20th week (1.14 ± 0.06, p 0.05). PERK and CHOP expressions were significantly higher than the control in the 15th (PERK = 1.30 ± 0.12, CHOP = 1.48 ± 0.23) and 20th weeks (PERK = 1.63 ± 0.20, CHOP = 1.67 ± 0.22, p 0.05). Conclusion: Upregulation of IRN1, PERK, ATF6, and CHOP demonstrates a strong ER stress response during colorectal cancer development.