Metastatic pancreatic neuroendocrine tumors have decreased somatostatin expression and increased Akt signaling.
Surgery
; 169(1): 155-161, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-32611516
BACKGROUND: Patients with pancreatic neuroendocrine tumors often present with metastases, which reduce survival. Molecular features associated with pancreatic neuroendocrine tumor tumorigenesis have been reported, but mechanisms of metastasis remain incompletely understood. METHODS: RNA sequencing was performed on primary and metastatic pancreatic neuroendocrine tumors from 43 patients. Differentially expressed genes were identified, and quantitative polymerase chain reaction used to confirm expression differences. BON cells were transfected with short interfering RNAs and short hairpin RNAs to create knockdowns. Expression changes were confirmed by quantitative polymerase chain reaction, cell viability assessed, and protein levels evaluated by Western blot and immunofluorescence. RESULTS: Nodal and hepatic metastases had decreased expression of somatostatin compared with primary tumors (P = .003). Quantitative polymerase chain reaction in a validation cohort confirmed 5.3-fold lower somatostatin expression in hepatic metastases (P = .043) with no difference in somatostatin receptor, synaptophysin, or chromogranin A expression. Somatostatin knockdown in BON cells increased cell metabolic activity, viability, and growth. Somatostatin-knockdown cells had significantly higher levels of phosphorylated Akt protein and higher mTOR compared with controls. CONCLUSION: Pancreatic neuroendocrine tumor metastases have lower expression of somatostatin than primary tumors, and somatostatin knockdown increased growth in pancreatic neuroendocrine tumor cell lines. This was associated with increased activation of Akt, identifying this pathway as a potential mechanism by which loss of somatostatin expression promotes the metastatic phenotype.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Somatostatina
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Tumores Neuroendocrinos
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Proteínas Proto-Oncogénicas c-akt
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Neoplasias Hepáticas
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Surgery
Año:
2021
Tipo del documento:
Article