Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines.
Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis.
Nielsen
Sonja K
SK
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Møllgård
Kjeld
K
Clement
Christian A
CA
Veland
Iben R
IR
Awan
Aashir
A
Yoder
Bradley K
BK
Novak
Ivana
I
Christensen
Søren Tvorup
ST
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002923:Cilia / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005333:Fetus / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014162:Transfection; D000075746:Zinc Finger Protein Gli2
C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D000075746:Zinc Finger Protein Gli2; D049452:Green Fluorescent Proteins