Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among patients with the rare diagnosis of pancreatic neuroendocrine tumor (P-NET), a substantial proportion suffer from the inherited cancer syndrome multiple endocrine neoplasia type 1 (MEN1), which is caused by germline mutations of the MEN1 suppressor gene. Somatic mutations and loss of the MEN1 protein (menin) are frequently also found in sporadic P-NETs. Thus, a human neuroendocrine pancreatic cell line with biallelic inactivation of MEN1 might be of value for studying tumorigenesis. We used the polyclonal human P-NET cell line BON1, which expresses menin, serotonin, chromogranin A and neurotensin, to generate a monoclonal stable MEN1 knockout BON1 cell line (MEN1-KO-BON1) by CRISPR/Cas9 editing. Changes in morphology, hormone secretion, and proliferation were analyzed, and proteomics were assessed using nanoLC-MS/MS and Ingenuity Pathway Analysis (IPA). The menin-lacking MEN1-KO-BON1 cells had increased chromogranin A production and were smaller, more homogenous, rounder and grew faster than their control counterparts. Proteomic analysis revealed 457 significantly altered proteins, and IPA identified biological functions related to cancer, e.g., posttranslational modification and cell death/survival. Among 39 proteins with at least a two-fold difference in expression, twelve are relevant in glucose homeostasis and insulin resistance. The stable monoclonal MEN1-KO-BON1 cell line was found to have preserved neuroendocrine differentiation, increased proliferation, and an altered protein profile.
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PMID:Generation and characterization of CRISPR/Cas9-mediated MEN1 knockout BON1 cells: a human pancreatic neuroendocrine cell line. 3288 6

BACKGROUND Pancreatic neuroendocrine tumors (P-NETs) are uncommon neoplasms, with few studies to date assessing serum biomarkers for the diagnosis of P-NETs. This study assessed the ability of serum chromogranin A (CgA) concentrations to distinguish P-NETs from other pancreatic lesions in a Chinese population and to determine the histological grades of P-NETs. MATERIAL AND METHODS This prospective study enrolled 165 patients, including 73 with proven P-NETs, 60 with malignant tumors of the pancreas, and 32 with benign lesions of the pancreas. Serum CgA concentrations were measured by ELISA. RESULTS Serum CgA concentrations were significantly higher in patients with P-NET than in patients with other pancreatic malignancies and benign lesions (P<0.001), but did not differ significantly in the latter 2 groups (P=0.827). Serum CgA concentrations were significantly higher in patients with non-insulinoma P-NETs than in the other groups (P<0.001), but did not differ significantly in patients with insulinoma and patients with non-P-NETs (P=0.668). Receiver operating characteristic (ROC) curves revealed that a serum CgA concentration of 77.8 ng/ml could distinguish patients with non-insulinoma P-NETs from patients with non-P-NETs, with a sensitivity of 96.7%, a specificity of 76.1%, and an area under the ROC curve of 0.897. In patients with P-NETs, multifactor analysis showed that the non-insulinoma subtype and the presence of liver metastases were associated with elevated serum CgA (both p<0.001). CONCLUSIONS Serum CgA concentration may be a valuable diagnostic biomarker for non-insulinoma P-NETs. Elevated serum CgA is likely associated with liver metastases.
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PMID:Chromogranin A: A Valuable Serum Diagnostic Marker for Non-Insulinoma Neuroendocrine Tumors of the Pancreas in a Chinese Population. 3314 11


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