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Zebrafish model of KRAS-initiated pancreatic endocrine tumor

Animal Cells and Systems 2019년 23권 3호 p.209 ~ 218
오세경, 박준태,
소속 상세정보
오세경 ( Oh Se-Kyung ) - Catholic Kwandong University College of Medicine Department of Medicine
박준태 ( Park Joon-Tae ) - Incheon National University Division of Life Sciences

Abstract


Pancreatic cancer constitutes a genetic disease in which somatic mutations in the KRAS proto-oncogene are detected in 95% of cases. Activation of the KRAS proto-oncogene represents an initiating event in pancreatic tumorigenesis. Here, we established a zebrafish pancreatic neoplasia model that recapitulates human pancreatic tumors. Toward this end, we generated a stable CRE/Lox-based zebrafish model system to express oncogenic KRASG12D in the elastase3I domain of the zebrafish pancreas. Lineage tracing experiments showed that early KRASG12D -responsive pancreatic progenitors contribute to endocrine in addition to exocrine cells. In this system, 10% and 40% of zebrafish developed pancreatic tumors by 6 and 12 months, respectively. The histological profiles of these experimental tumors bore a striking resemblance to those of pancreatic endocrine tumors. Immunohistochemical analysis including the endocrine cell-specific marker confirmed the pancreatic tumor region as a characteristic endocrine tumor. Taken together, our zebrafish model data revealed that pancreatic endocrine tumors originate from early KRASG12D -responsive pancreatic progenitor cells. These findings demonstrated that this zebrafish model may be suitable as an experimental and preclinical system to evaluate different strategies for targeting pancreatic endocrine tumors and ultimately improve the outcome for patients with pancreatic endocrine tumors.

키워드

Pancreatic endocrine tumor; zebrafish; KRAS

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