Abstract
Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant. Efficient control of cancer growth may substantially improve the survival of PDAC patients. However, no efficient treatments are so far available. Here, we inhibited transforming growth factor β (TGFβ) receptor signaling by overexpression of a key inhibitor of this pathway, SMAD7, in the mouse pancreas, using a recently developed intraductal infusion method. Overexpression of SMAD7 significantly increased growth of both implanted PDAC and PDAC by K-ras modification. Our data thus suggest that TGFβ receptor signaling restrains growth of PDAC, and modulation of TGFβ receptor signaling may be an effective treatment for PDAC.
Keywords:
Cancer growth; Intraductal infusion; Pancreatic ductal adenocarcinoma (PDAC); TGFβ.
MeSH terms
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Animals
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Apoptosis
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Carcinoma, Pancreatic Ductal / metabolism
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Carcinoma, Pancreatic Ductal / pathology
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Carcinoma, Pancreatic Ductal / prevention & control*
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Cell Proliferation
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Gene Expression Regulation, Neoplastic*
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Humans
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Immunoenzyme Techniques
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / prevention & control*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / antagonists & inhibitors*
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism
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Smad7 Protein / metabolism
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Transforming Growth Factor beta / metabolism
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Receptors, Transforming Growth Factor beta
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Smad7 Protein
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Smad7 protein, mouse
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Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II