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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, METHODS, RESULTS. Meshes: Adolescent, Adult, Aged, Cell Cycle Proteins, Chronic Disease, Down-Regulation, Dual Specificity Phosphatase 1, Epidermal Growth Factor, Female, Gene Expression Regulation, Enzymologic, Humans, Immediate-Early Proteins, JNK Mitogen-Activated Protein Kinases, Male, Middle Aged, Mitogen-Activated Protein Kinases, Pancreas, Pancreatic Neoplasms, Pancreatitis, Phosphoprotein Phosphatases, Phosphorylation, Protein Phosphatase 1, Protein Tyrosine Phosphatases, RNA, Messenger, Transfection, Tumor Cells, Cultured.
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Does down-regulation of the dual-specificity phosphatase MKP-1 suppress tumorigenicity of pancreatic cancer cells? Context: In both pancreatic cancer and chronic pancreatitis, there is enhanced expression of mitogenic growth factors and their tyrosine kinase receptors, which have the capacity to activate mitogen-activated protein kinase (MAPK). In view of the important role of MAPK kinase phosphatase (MKP)-1 in the regulation of MAPK activation, the expression and functional role of MKP-1 was analyzed. Pancreatic tissues were analyzed by Northern blotting, Western blotting, and immunohistochemistry. Pancreatic cancer cells were transfected with a full-length MKP-1 antisense construct. Growth characteristics and tumorigenicity in vivo and the effects of mitogenic growth factors on cell growth and MAPK activation were determined in transfected and control cells. MKP-1 messenger RNA (mRNA) levels were increased in pancreatic cancer and chronic pancreatitis (CP) tissues. Moderate to strong MKP-1 immunoreactivity was present in the cancer cells, ductal cells of pancreatic intraepithelial neoplasia, and in tubular complexes in CP. Down-regulation of MKP-1 resulted in decreased anchorage-dependent and -independent growth of pancreatic cancer cells, and decreased tumorigenicity in a nude mouse tumor model. MKP-1 down-regulation led to decreased proliferation and sustained MAPK activation in response to mitogens.
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Suppression of MKP-1 expression reduces the tumorigenicity of pancreatic cancer cells in vivo, suggesting that MKP-1 contributes to enhanced mitogenic signaling in pancreatic cancer cells. Final Decision: yes