Regulation of tight junctions in human normal pancreatic duct epithelial cells and cancer cells.
To investigate the regulation of tight junction molecules in normal human pancreatic duct epithelial (HPDE) cells and pancreatic cancer cells, we introduced the human telomerase reverse transcriptase (hTERT) gene into HPDE cells in primary culture and compared them to pancreatic cancer cell lines. The hTERT-transfected HPDE cells were positive for PDE markers and expressed claudin-1, claudin-4, claudin-7, and claudin-18, occludin, tricellulin, marvelD3, JAM-A, zonula occludens (ZO)-1, and ZO-2. The tight junction molecules, including claudin-4 and claudin-18 of normal HPDE cells, were in part regulated via a protein kinase C signal pathway by transcriptional control. In addition, claudin-18 in normal HPDE cells and pancreatic cancer cells was markedly induced by a PKC activator, and claudin-18 in pancreatic cancer cells was also modified by DNA methylation. In the marvel family of normal HPDE cells and pancreatic cancer cells, tricellulin was upregulated via a c-Jun N-terminal kinase pathway, and marvelD3 was downregulated during Snail-induced epithelial-mesenchymal transition.
Department of Pathology, Sapporo Medical University School of Medicine, Japan. ktakashi@sapmed.ac.jp
Takashi
T
Kojima
Norimasa
N
Sawada
D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D057167:Claudins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D062794:MARVEL Domain Containing 2 Protein / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism*
D057167:Claudins; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; C548163:MARVELD3 protein, human; D008565:Membrane Proteins; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; C509186:TERT protein, human; D019098:Telomerase