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expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
by
Tang, Daolin
, Livesey, Kristen M
, Zeh, Herbert J. III
, Lotze, Michael T
, Loux, Tara
, Kang, Rui
, Schapiro, Nicole E
, Vernon, Philip
, Krasinskas, Alyssa
in
adenosine triphosphate
/ Adenosine Triphosphate - biosynthesis
/ Anger
/ animal models
/ Animals
/ Apoptosis
/ Autophagy
/ Biological Sciences
/ biosynthesis
/ Carcinogenesis
/ Cell growth
/ Cell Line, Tumor
/ chemotherapy
/ Cytokines
/ deficiency
/ drug therapy
/ etiology
/ Gene expression
/ genetics
/ glycation
/ Humans
/ immunology
/ interleukin-6
/ Interleukin-6 - metabolism
/ Lesions
/ metabolism
/ metastasis
/ Mice
/ Mice, 129 Strain
/ Mice, Inbred C57BL
/ Mice, Mutant Strains
/ Mice, Transgenic
/ Mitochondria
/ Mitochondria - metabolism
/ Mutation
/ Neoplasia
/ oncogenes
/ Pancreatic cancer
/ Pancreatic neoplasms
/ Pancreatic Neoplasms - etiology
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - immunology
/ Pancreatic Neoplasms - metabolism
/ Phosphorylation
/ physiology
/ Proto-Oncogene Proteins p21(ras)
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Receptor for Advanced Glycation End Products
/ Receptors, Immunologic
/ Receptors, Immunologic - deficiency
/ Receptors, Immunologic - genetics
/ Receptors, Immunologic - metabolism
/ Rodents
/ Signal Transduction
/ STAT3 Transcription Factor
/ STAT3 Transcription Factor - metabolism
/ transcription factors
/ Transducers
/ Tumor Microenvironment
/ Tumor Microenvironment - genetics
/ Tumor Microenvironment - immunology
/ Tumor Microenvironment - physiology
/ Tumors
2012
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expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
by
Tang, Daolin
, Livesey, Kristen M
, Zeh, Herbert J. III
, Lotze, Michael T
, Loux, Tara
, Kang, Rui
, Schapiro, Nicole E
, Vernon, Philip
, Krasinskas, Alyssa
in
adenosine triphosphate
/ Adenosine Triphosphate - biosynthesis
/ Anger
/ animal models
/ Animals
/ Apoptosis
/ Autophagy
/ Biological Sciences
/ biosynthesis
/ Carcinogenesis
/ Cell growth
/ Cell Line, Tumor
/ chemotherapy
/ Cytokines
/ deficiency
/ drug therapy
/ etiology
/ Gene expression
/ genetics
/ glycation
/ Humans
/ immunology
/ interleukin-6
/ Interleukin-6 - metabolism
/ Lesions
/ metabolism
/ metastasis
/ Mice
/ Mice, 129 Strain
/ Mice, Inbred C57BL
/ Mice, Mutant Strains
/ Mice, Transgenic
/ Mitochondria
/ Mitochondria - metabolism
/ Mutation
/ Neoplasia
/ oncogenes
/ Pancreatic cancer
/ Pancreatic neoplasms
/ Pancreatic Neoplasms - etiology
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - immunology
/ Pancreatic Neoplasms - metabolism
/ Phosphorylation
/ physiology
/ Proto-Oncogene Proteins p21(ras)
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Receptor for Advanced Glycation End Products
/ Receptors, Immunologic
/ Receptors, Immunologic - deficiency
/ Receptors, Immunologic - genetics
/ Receptors, Immunologic - metabolism
/ Rodents
/ Signal Transduction
/ STAT3 Transcription Factor
/ STAT3 Transcription Factor - metabolism
/ transcription factors
/ Transducers
/ Tumor Microenvironment
/ Tumor Microenvironment - genetics
/ Tumor Microenvironment - immunology
/ Tumor Microenvironment - physiology
/ Tumors
2012
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expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
by
Tang, Daolin
, Livesey, Kristen M
, Zeh, Herbert J. III
, Lotze, Michael T
, Loux, Tara
, Kang, Rui
, Schapiro, Nicole E
, Vernon, Philip
, Krasinskas, Alyssa
in
adenosine triphosphate
/ Adenosine Triphosphate - biosynthesis
/ Anger
/ animal models
/ Animals
/ Apoptosis
/ Autophagy
/ Biological Sciences
/ biosynthesis
/ Carcinogenesis
/ Cell growth
/ Cell Line, Tumor
/ chemotherapy
/ Cytokines
/ deficiency
/ drug therapy
/ etiology
/ Gene expression
/ genetics
/ glycation
/ Humans
/ immunology
/ interleukin-6
/ Interleukin-6 - metabolism
/ Lesions
/ metabolism
/ metastasis
/ Mice
/ Mice, 129 Strain
/ Mice, Inbred C57BL
/ Mice, Mutant Strains
/ Mice, Transgenic
/ Mitochondria
/ Mitochondria - metabolism
/ Mutation
/ Neoplasia
/ oncogenes
/ Pancreatic cancer
/ Pancreatic neoplasms
/ Pancreatic Neoplasms - etiology
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - immunology
/ Pancreatic Neoplasms - metabolism
/ Phosphorylation
/ physiology
/ Proto-Oncogene Proteins p21(ras)
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Receptor for Advanced Glycation End Products
/ Receptors, Immunologic
/ Receptors, Immunologic - deficiency
/ Receptors, Immunologic - genetics
/ Receptors, Immunologic - metabolism
/ Rodents
/ Signal Transduction
/ STAT3 Transcription Factor
/ STAT3 Transcription Factor - metabolism
/ transcription factors
/ Transducers
/ Tumor Microenvironment
/ Tumor Microenvironment - genetics
/ Tumor Microenvironment - immunology
/ Tumor Microenvironment - physiology
/ Tumors
2012
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expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
Journal Article
expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia
2012
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Overview
Pancreatic cancer is an almost uniformly lethal disease, characterized by late diagnosis, early metastasis, resistance to chemotherapy, and early mutation of the Kras oncogene. Here we show that the receptor for advanced glycation endproducts (RAGE) is required for the activation of interleukin 6 (IL-6)–mediated mitochondrial signal transducers and activators of transcription 3 (STAT3) signaling in pancreatic carcinogenesis. RAGE expression correlates with elevated levels of autophagy in pancreatic cancer in vivo and in vitro, and this heightened state of autophagy is required for IL-6–induced STAT3 activation. To further explore the intersection of RAGE, autophagy, and pancreatic carcinogenesis, we created a transgenic murine model, backcrossing RAGE-null mice to a spontaneous mouse model of pancreatic cancer, Pdx1-Cre:KrasG12D/+ (KC). Targeted ablation of Rage in KC mice delayed neoplasia development, decreased levels of autophagy, and inhibited mitochondrial STAT3 activity and subsequent ATP production. Our results suggest a critical role for RAGE expression in the earliest stages of pancreatic carcinogenesis, potentially acting as the \"autophagic switch,\" regulating mitochondrial STAT3 signaling.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Adenosine Triphosphate - biosynthesis
/ Anger
/ Animals
/ etiology
/ genetics
/ Humans
/ Lesions
/ Mice
/ Mutation
/ Pancreatic Neoplasms - etiology
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - immunology
/ Pancreatic Neoplasms - metabolism
/ Proto-Oncogene Proteins p21(ras)
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Receptor for Advanced Glycation End Products
/ Receptors, Immunologic - deficiency
/ Receptors, Immunologic - genetics
/ Receptors, Immunologic - metabolism
/ Rodents
/ STAT3 Transcription Factor - metabolism
/ Tumor Microenvironment - genetics
/ Tumor Microenvironment - immunology
/ Tumor Microenvironment - physiology
/ Tumors
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