Abstract 3922: Deregulated thymidylate synthase promotes tumorigenecity in pancreatic neuroendocrine tumors
| Autor: | Min Chen, Hye Seung Lee, Maria Zajac-Kaye, Kyungah Maeng |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
congenital hereditary and neonatal diseases and abnormalities endocrine system Cancer Research geography Pathology medicine.medical_specialty geography.geographical_feature_category endocrine system diseases biology Cancer Neuroendocrine tumors Islet medicine.disease medicine.disease_cause Thymidylate synthase medicine.anatomical_structure Oncology Cancer research medicine Carcinoma biology.protein Pancreas Carcinogenesis |
| Zdroj: | Cancer Research. 74:3922-3922 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2014-3922 |
| Popis: | The incidence of pancreatic neuroendocrine tumors (PNET) is rapidly increasing and the prevalence in the US is now estimated to be over 100,000. The lack of a suitable animal model that recapitulates the human disease has limited development of new treatment for PNET. We established a new mouse model by taking advantage of our discovery that elevated levels of Thymidylate Synthase (TS) plays a direct causal role in tumorigenesis in vitro and that overexpression of human TS (hTS) in transgenic mice promotes development of adenomas in the endocrine pancreas. We crossed hTS transgenic mice with conditional MEN1 null mice that were previously shown to develop pancreatic islet carcinoma upon long latency. MEN1 was recently shown to be the most commonly mutated tumor suppressor gene in sporadic PNETs (44% of PNET patients have MEN1 mutations). Our newly established hTS/MEN1 mice model developed aggressive PNET with 100% penetrance due to overexpressed TS in MEN1 null mice. Transgenic overexpression of TS induced islet carcinoma with shortened latency as compared to MEN1-/- mice. The hTS/fMen1-/- mice develop islet carcinoma as early as 6 month of age whereas MEN1-/- mice develop islet carcinoma at 8 months of age. The median age of onset of islet carcinoma in hTS/MEN1-/- and MEN1-/- mice was 10.38±2.45 vs. 13.06±0.48 months; p Citation Format: Kyungah Maeng, Hye Seung Lee, Min Chen, Maria Zajac-Kaye. Deregulated thymidylate synthase promotes tumorigenecity in pancreatic neuroendocrine tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3922. doi:10.1158/1538-7445.AM2014-3922 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|