Zebrafish model of KRAS-initiated pancreatic cancer
Pancreatic cancer constitutes a genetic disease in which somatic mutations in the KRAS proto-oncogene are detected in a majority of tumors. KRAS mutations represent an early event during pancreatic tumorigenesis that crucial for cancer initiation and progression. Here, we established a zebrafish pan...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-11-01
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| Series: | Animal Cells and Systems |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19768354.2018.1530301 |
| _version_ | 1811284602281525248 |
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| author | Joon Tae Park Steven D. Leach |
| author_facet | Joon Tae Park Steven D. Leach |
| author_sort | Joon Tae Park |
| collection | DOAJ |
| description | Pancreatic cancer constitutes a genetic disease in which somatic mutations in the KRAS proto-oncogene are detected in a majority of tumors. KRAS mutations represent an early event during pancreatic tumorigenesis that crucial for cancer initiation and progression. Here, we established a zebrafish pancreatic cancer model that highly recapitulates human pancreatic intraepithelial neoplasia (PanIN) development. We established a novel system combining CRE/Lox technology with the GAL4/UAS system to express oncogenic KRAS in the ptf1a domain temporarily. In this system, zebrafish developed PanIN at an 11.1% rate by 24 and 36 weeks after KRASG12V induction. The histological and immunohistochemical profiles of these experimental tumors bore striking resemblance to human PanIN. Within the whole abnormal area, the entire spectrum of differentiation ranging from PanIN-1 to PanIN-3 was noted. Immunohistochemical analysis including Alcian blue, CK-18, cadhedrin-1, and DCLK1 staining confirmed the PanIN region as a characteristic pancreatic cancer precursor lesion. Taken together, these findings demonstrate that this zebrafish model may offer the possibility of an experimental and preclinical system to evaluate different strategies for targeting pancreatic tumors and finally improve the outcome for the patients with pancreatic tumors. |
| first_indexed | 2024-04-13T02:31:13Z |
| format | Article |
| id | doaj.art-6b019a2d44ab4242a6b88b3807899f95 |
| institution | Directory Open Access Journal |
| issn | 1976-8354 2151-2485 |
| language | English |
| last_indexed | 2024-04-13T02:31:13Z |
| publishDate | 2018-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Animal Cells and Systems |
| spelling | doaj.art-6b019a2d44ab4242a6b88b3807899f952022-12-22T03:06:33ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852018-11-0122635335910.1080/19768354.2018.15303011530301Zebrafish model of KRAS-initiated pancreatic cancerJoon Tae Park0Steven D. Leach1Incheon National UniversityNorris Cotton Cancer Center, Geisel School of Medicine at DartmouthPancreatic cancer constitutes a genetic disease in which somatic mutations in the KRAS proto-oncogene are detected in a majority of tumors. KRAS mutations represent an early event during pancreatic tumorigenesis that crucial for cancer initiation and progression. Here, we established a zebrafish pancreatic cancer model that highly recapitulates human pancreatic intraepithelial neoplasia (PanIN) development. We established a novel system combining CRE/Lox technology with the GAL4/UAS system to express oncogenic KRAS in the ptf1a domain temporarily. In this system, zebrafish developed PanIN at an 11.1% rate by 24 and 36 weeks after KRASG12V induction. The histological and immunohistochemical profiles of these experimental tumors bore striking resemblance to human PanIN. Within the whole abnormal area, the entire spectrum of differentiation ranging from PanIN-1 to PanIN-3 was noted. Immunohistochemical analysis including Alcian blue, CK-18, cadhedrin-1, and DCLK1 staining confirmed the PanIN region as a characteristic pancreatic cancer precursor lesion. Taken together, these findings demonstrate that this zebrafish model may offer the possibility of an experimental and preclinical system to evaluate different strategies for targeting pancreatic tumors and finally improve the outcome for the patients with pancreatic tumors.http://dx.doi.org/10.1080/19768354.2018.1530301Pancreatic cancerPanINzebrafishKRAS |
| spellingShingle | Joon Tae Park Steven D. Leach Zebrafish model of KRAS-initiated pancreatic cancer Animal Cells and Systems Pancreatic cancer PanIN zebrafish KRAS |
| title | Zebrafish model of KRAS-initiated pancreatic cancer |
| title_full | Zebrafish model of KRAS-initiated pancreatic cancer |
| title_fullStr | Zebrafish model of KRAS-initiated pancreatic cancer |
| title_full_unstemmed | Zebrafish model of KRAS-initiated pancreatic cancer |
| title_short | Zebrafish model of KRAS-initiated pancreatic cancer |
| title_sort | zebrafish model of kras initiated pancreatic cancer |
| topic | Pancreatic cancer PanIN zebrafish KRAS |
| url | http://dx.doi.org/10.1080/19768354.2018.1530301 |
| work_keys_str_mv | AT joontaepark zebrafishmodelofkrasinitiatedpancreaticcancer AT stevendleach zebrafishmodelofkrasinitiatedpancreaticcancer |