Pancreatic Cell News Volume 5.28 | Jul 29 2014

Mnk1 Is a Novel Acinar Cell-Specific Kinase Required for Exocrine Pancreatic Secretion and Response to Pancreatitis in Mice
Scientists investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. [Gut] Abstract

The Nuclear Hormone Receptor Family Member NR5A2 Controls Aspects of Multipotent Progenitor Cell-Formation and Acinar Differentiation during Pancreatic Organogenesis
Researchers show that Nr5a2 plays crucial regulatory roles during organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the expansion of the nascent pancreatic epithelium, for the subsequent formation of the multipotent progenitor cell population that gives rise to pre-acinar cells and bipotent cells with ductal and islet endocrine potential, and for the formation and differentiation of acinar cells. [Development] Abstract

GLP-1 Analog Liraglutide Enhances Proinsulin Processing in Pancreatic β-Cells via a PKA-Dependent Pathway
In cultured mouse pancreatic β-cell line Min6, liraglutide stimulated prohormone convertase (PC) 1/3 and PC2 expression and lowered the proinsulin/insulin ratio in a dose- and time-dependent manner. [Endocrinology] Abstract

Pdx1 and USF Transcription Factors Coordinately Regulate Alx3 Gene Expression in Pancreatic β Cells
Researchers investigated the mechanisms that regulate expression of Alx3 in pancreatic islets at the transcriptional level. They found that the Alx3 promoter contains at least eight putative regulatory elements with an E-box consensus sequence, three of which were determined to be functional and required for Alx3 promoter activity by mutational analysis in transfected MIN6 b cells. [Biochem J] Abstract

Gluco-Incretins Regulate Beta-Cell Glucose Competence by Epigenetic Silencing of Fxyd3 Expression
Scientists searched for genes that were differentially expressed in islets from control and Glp1r^−/−; Gipr^−/− mice, which show reduced glucose competence. Overexpression and knockdown studies; insulin secretion analysis; analysis of gene expression in islets from control and diabetic mice and humans as well as gene methylation and transcriptional analysis were performed. [PLoS One] Full Article

PANCREATIC CANCER

Mechanistic Evaluation of QD232 in Pancreatic Cancer
Researchers identified a novel small-molecule, QD232 that potently decreases Src/FAK and STAT3 phosphorylation resulting in decreased cancer cell viability and migration. [Br J Pharmacol] Abstract

Rottlerin Suppresses Growth of Human Pancreatic Tumors in Nude Mice, and Pancreatic Cancer Cells Isolated from Kras^G12D Mice
Researchers examined the molecular mechanisms by which rottlerin inhibited growth of human pancreatic tumors in Balb C nude mice, and pancreatic cancer cells isolated from Kras^G12D mice. [Cancer Lett] Abstract

Cooperativity of Oncogenic K-Ras and Downregulated p16/INK4A in Human Pancreatic Tumorigenesis
Scientists investigated the role of p16 in hTERT-immortalized human pancreatic epithelial nestin-expressing (HPNE) cells expressing mutant K-ras. They found that expression of p16 was induced by oncogenic K-ras in these HPNE cells and that silencing of this induced p16 expression resulted in tumorigenic transformation and development of metastatic pancreatic epithelial adenocarcinoma in an orthotopic xenograft mouse model. [PLoS One] Full Article

The Cytotoxic Role of RREB1, ZIP3 Zinc Transporter, and Zinc in Human Pancreatic Adenocarcinoma
Researchers demonstrate that exposure of Panc1 cells to physiological concentrations of zinc that result in increased zinc uptake and accumulation also inhibits cell proliferation. The authors further show that ZIP3 is the important transporter required for the accumulation of zinc and its inhibition of proliferation. [Cancer Biol Ther] Abstract

Secreted Protein Acidic and Rich in Cysteine Inhibits the Growth of Human Pancreatic Cancer Cells with G1 Arrest Induction
Scientists found that secreted protein acidic and rich in cysteine expression was weak in cancer cells in specimens which negatively correlated with the expression level of phosphorylated pRB and poorer outcome. [Tumor Biol] Abstract

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Halozyme Resumes Patient Enrollment and Dosing in PEGPH20 Clinical Program in Pancreatic Cancer
Halozyme Therapeutics, Inc. announced that it has resumed enrollment and dosing of patients in its ongoing Phase II trial evaluating PEGPH20 in patients with pancreatic cancer under the revised clinical protocol agreed to with the FDA. [Halozyme Therapeutics, Inc.] Press Release

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NEW Postdoctoral Positions – Diabetes Research (Sanofi)

NEW Principal Scientist – Diabetes Biology (Novo Nordisk China R&D Center)

Postdoctoral Research Assistant – Chimeric Antigen Receptor (CAR) T-Cell Immunotherapy for Pancreatic Cancer Stem Cells (Queen Mary University of London)

Professorship – Molecular Mechanisms of Diabetes Pathogenesis (University of Southern Denmark)

Postdoctoral Fellow – Metabolism (University of Copenhagen)

PhD Scholarships – Diabetes (Danish Diabetes Academy)

Diabetes UK RD Lawrence Fellowships (Diabetes UK)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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