Characterization of primary cilia and hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

被引:49
|
作者
Nielsen, Sonja K.
Mollgard, Kjeld [2 ]
Clement, Christian A.
Veland, Iben R.
Awan, Aashir
Yoder, Bradley K. [3 ]
Novak, Ivana
Christensen, Soren Tvorup [1 ]
机构
[1] Univ Copenhagen, Dept Biol, Sect Cell & Dev Biol, DK-2100 Copenhagen OE, Denmark
[2] Univ Copenhagen, Panum Inst, Dept Cellular & Mol Med, DK-2100 Copenhagen OE, Denmark
[3] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA
关键词
primary cilia; pancreas; exocrine duct; development; cancer; Hedgehog signaling; Smoothened; Patched; Gli2; Gli3;
D O I
10.1002/dvdy.21610
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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.
引用
收藏
页码:2039 / 2052
页数:14
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