BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice

Chenxi Gao; Farzad Esni; Edward Chu; Jing Hu

doi:10.1016/j.bbrep.2023.101634

BRAF^V600E mutation and DSS treatment synergize to induce cecal tumor formation in mice

Biochem Biophys Rep. 2024 Jan 1:37:101634. doi: 10.1016/j.bbrep.2023.101634. eCollection 2024 Mar.

Authors

Chenxi Gao^{1

2}, Farzad Esni³, Edward Chu⁴, Jing Hu^{1

2}

Affiliations

¹ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
² UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
³ Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
⁴ Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

Abstract

BRAF mutation is a driver mutation in colorectal cancer (CRC), and BRAF^V600E mutation is found in 10-15 % of all CRCs. BRAF mutant CRCs in patients are primarily localized in the right colon, including the cecum. However, in the Vill-Cre;BRAF^V600E/+ mice, adenomas mainly developed in the small intestines of the mice, and no tumor formed in the cecum. The mice model of BRAF^V600E-mutant CRC with tumors in the cecum is lacking. Dextran Sulfate Sodium (DSS) treatment induces colitis in mice. Acute DSS treatment does not lead to tumor formation. We show that DSS treatment and BRAF^V600E mutation synergistically induced cecal tumorigenesis, and cecal tumors formed within three months after five-day DSS treatment. The location of the adenomas supports the patient relevance of the model. Our BRAF^V600E/DSS model provides a valuable in vivo model for future identification and validation of novel therapeutic approaches for treating BRAF-mutant CRC. Our results are consistent with the notion that BRAF^V600E mutation is an oncogenic event that can shift controlled regeneration to unrestrained oncogenesis.

Keywords: BRAFV600E mutation; CRC; DSS.