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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Adenocarcinoma, Animals, Antimetabolites, Antineoplastic, Apoptosis, Blotting, Western, Carcinoma, Pancreatic Ductal, Caspase 3, Cells, Cultured, Deoxycytidine, Drug Resistance, Neoplasm, Enzyme Activation, HMGA1a Protein, Humans, Immunoenzyme Techniques, Male, Mice, Mice, Nude, Pancreatic Neoplasms, Proto-Oncogene Proteins c-akt, RNA Interference, Signal Transduction, Tumor Cells, Cultured.
user
Is hMGA1 a molecular determinant of chemoresistance to gemcitabine in pancreatic adenocarcinoma? Context: HMGA1 proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. We previously have shown that RNA interference targeting the HMGA1 gene may represent a potential chemosensitizing strategy in pancreatic adenocarcinoma cells. In this study, we tested the hypothesis that HMGA1 promotes chemoresistance to gemcitabine in pancreatic cancer cells. Stable short hairpin RNA-mediated HMGA1 silencing in BxPC3 and MiaPaCa2 cells promoted chemosensitivity to gemcitabine, with reductions in gemcitabine IC(50) and increases in gemcitabine-induced apoptosis and caspase-3 activation. In contrast, forced HMGA1 overexpression in MiaPaCa2 cells promoted chemoresistance to gemcitabine, with increases in gemcitabine IC(50) and reductions in gemcitabine-induced apoptosis and caspase-3 activation. Dominant negative Akt abrogated HMGA1 overexpression-induced increases in chemoresistance to gemcitabine. Finally, HMGA1 silencing promoted chemosensitivity to gemcitabine in vivo in a nude mouse xenograft model of pancreatic adenocarcinoma.
assistant
Our findings suggest that HMGA1 promotes chemoresistance to gemcitabine through an Akt-dependent mechanism. Targeted therapies directed at HMGA1 represent a potential strategy for ameliorating chemoresistance in pancreatic adenocarcinoma. Final Decision: yes