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RAGE upregulation confers a proliferative phenotype to PANC‐1 pancreatic cancer cells
Author(s) -
Swami Priyanka,
Vetter Stefan W.,
Leclerc Estelle
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.670.12
Subject(s) - rage (emotion) , pancreatic cancer , cancer research , glycation , downregulation and upregulation , metastasis , cancer cell , cell growth , signal transduction , biology , transfection , autophagy , cancer , apoptosis , medicine , receptor , microbiology and biotechnology , immunology , cell culture , neuroscience , gene , biochemistry , genetics
Pancreatic cancer is one of the deadliest cancer and is characterized by late diagnosis, aggressive clinical course and resistance to existing therapies. Recent efforts have been concentrated on identifying new targets and molecular pathways which contribute to the development and progression of this lethal disease, and which could be used to establish new therapeutic approaches. Several reports have shown that the Receptor for Advanced Glycation End products (RAGE) contributes to the progression of pancreatic cancer. RAGE is demonstrated to be involved in processes like apoptosis, autophagy, and tumor cell bioenergetics. It is reported that RAGE is required for optimal mitochondrial function in tumors for ATP production. However, the effect of RAGE expression on the proliferative and migratory properties of pancreatic cancer cells is currently not known. A better understanding of the mechanisms of RAGE signaling could lead to the development of new therapeutic strategies in pancreatic cancer. Our objective was to investigate the effect of RAGE up‐regulation on the proliferation and migration properties of the PANC‐1 pancreatic cancer cell‐line. We generated cells that overexpress RAGE four‐fold compared to non‐transfected cells. We then compared the proliferation, migration and invasion properties of the new cells with those of the wild‐type cells. We also compared the signaling pathways affected by RAGE overexpression in these cells. We showed that four‐fold up‐regulation of RAGE in PANC‐1 cells resulted in increased cell proliferation to the expenses of cell migration. Both Boyden chamber and wound healing supported the reduced migratory properties of the RAGE overexpressing cells. Further analysis showed significantly reduced levels of integrins in the RAGE transfected cells. We suggest that in the PANC‐1 cells, which exhibit a mixed epithelial – mesenchymal phenotype, RAGE expression switches the phenotypic balance toward a proliferative phenotype. We are currently exploring how RAGE up‐regulation affects the expression of its ligands in these cells. Support or Funding Information This work is partially supported by the National Institutes of Health grant 1P20GM109024 and the NDSU College of Health Professions.