BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice
BRAF mutation is a driver mutation in colorectal cancer (CRC), and BRAFV600E 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;BRAFV600E/+ mice, adenomas mainly developed in the small intes...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580823002157 |
| _version_ | 1797317105427677184 |
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| author | Chenxi Gao Farzad Esni Edward Chu Jing Hu |
| author_facet | Chenxi Gao Farzad Esni Edward Chu Jing Hu |
| author_sort | Chenxi Gao |
| collection | DOAJ |
| description | BRAF mutation is a driver mutation in colorectal cancer (CRC), and BRAFV600E 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;BRAFV600E/+ mice, adenomas mainly developed in the small intestines of the mice, and no tumor formed in the cecum. The mice model of BRAFV600E-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 BRAFV600E 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 BRAFV600E/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 BRAFV600E mutation is an oncogenic event that can shift controlled regeneration to unrestrained oncogenesis. |
| first_indexed | 2024-03-08T03:30:02Z |
| format | Article |
| id | doaj.art-226cf0b55c064242b0d219a745172959 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-03-08T03:30:02Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-226cf0b55c064242b0d219a7451729592024-02-11T05:11:19ZengElsevierBiochemistry and Biophysics Reports2405-58082024-03-0137101634BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in miceChenxi Gao0Farzad Esni1Edward Chu2Jing Hu3Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA; UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USADepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USAAlbert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USADivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA; UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA; Corresponding author. 2.27 UPMC Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.BRAF mutation is a driver mutation in colorectal cancer (CRC), and BRAFV600E 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;BRAFV600E/+ mice, adenomas mainly developed in the small intestines of the mice, and no tumor formed in the cecum. The mice model of BRAFV600E-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 BRAFV600E 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 BRAFV600E/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 BRAFV600E mutation is an oncogenic event that can shift controlled regeneration to unrestrained oncogenesis.http://www.sciencedirect.com/science/article/pii/S2405580823002157BRAFV600E mutationDSSCRC |
| spellingShingle | Chenxi Gao Farzad Esni Edward Chu Jing Hu BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice Biochemistry and Biophysics Reports BRAFV600E mutation DSS CRC |
| title | BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice |
| title_full | BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice |
| title_fullStr | BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice |
| title_full_unstemmed | BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice |
| title_short | BRAFV600E mutation and DSS treatment synergize to induce cecal tumor formation in mice |
| title_sort | brafv600e mutation and dss treatment synergize to induce cecal tumor formation in mice |
| topic | BRAFV600E mutation DSS CRC |
| url | http://www.sciencedirect.com/science/article/pii/S2405580823002157 |
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