Unfolded protein response during the progression of colorectal carcinogenesis.

Acta cirurgica brasileira Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI:10.1590/acb400725

Cesar Augusto Sobrinho, Alexandre Moreira de Almeida, Maytana Roberta Taschin Grigolo, Michele Selzler, Antônio Carlos de Abreu, Letícia Silva Fagundes, Almir Souza Martins, Durval Batista Palhares, Rondon Tosta Ramalho

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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.

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结直肠癌发生过程中未折叠蛋白的反应。

目的：探讨大肠癌发生过程中内质网应激的分子演化。方法：56只无毛小鼠随机分为两组：对照组（不干预）；致癌性（在第三周和第四周用两剂10 mg/kg的偶氮氧甲烷治疗，在第二周、第五周和第八周用2.5%的葡聚糖硫酸钠治疗7天）。安乐死发生在第5周、第10周、第15周和第20周。收集结肠，通过实时定量聚合酶链反应检测内质网应激标志物（IRE1-α、PERK、ATF6、CHOP）的基因表达。结果：ERN1表达在第10周（1.39±0.16,p 0.05）和第20周（1.15±0.04,p 0.01）显著高于对照组。ATF6表达在第10周（1.71±0.29,p 0.05）和第20周（1.14±0.06,p 0.05）均有显著性差异。第15周（PERK = 1.30±0.12,CHOP = 1.48±0.23）和第20周（PERK = 1.63±0.20,CHOP = 1.67±0.22,p 0.05）， PERK和CHOP的表达均显著高于对照组。结论：IRN1、PERK、ATF6和CHOP的上调在结直肠癌的发展过程中表现出强烈的内质网应激反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Acta cirurgica brasileira

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