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Hedgehog signaling pathway is inactive in colorectal cancer cell lines
Author(s) -
Chatel Guillaume,
Ganeff Corine,
Boussif Naima,
Delacroix Laurence,
Briquet Alexandra,
Nolens Gregory,
Winkler Rosita
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22998
Subject(s) - cyclopamine , hedgehog signaling pathway , gli1 , cancer research , hedgehog , colorectal cancer , signal transduction , gli2 , biology , cell culture , cell growth , downregulation and upregulation , cell , pi3k/akt/mtor pathway , cancer , microbiology and biotechnology , chemistry , gene , genetics
The Hedgehog (Hh) signaling pathway plays an important role in human development. Abnormal activation of this pathway has been observed in several types of human cancers, such as the upper gastro‐intestinal tract cancers. However, activation of the Hh pathway in colorectal cancers is controversial. We analyzed the expression of the main key members of the Hh pathway in 7 colon cancer cell lines in order to discover whether the pathway is constitutively active in these cells. We estimated the expression of SHH, IHH, PTCH, SMO, GLI 1, GLI 2, GLI 3, SUFU and HHIP genes by RT‐PCR. Moreover, Hh ligand, Gli3 and Sufu protein levels were quantified by western blotting. None of the cell lines expressed the complete set of Hh pathway members. The ligands were absent from Colo320 and HCT116 cells, Smo from Colo205, HT29 and WiDr. GLI 1 gene was not expressed in SW480 cells nor were GLI 2/GLI 3 in Colo205 or Caco‐2 cells. Furthermore the repressive form of Gli3, characteristic of an inactive pathway, was detected in SW480 and Colo320 cells. Finally treatment of colon cancer cells with cyclopamine, a specific inhibitor of the Hh pathway, did not downregulate PTCH and GLI 1 genes expression in the colorectal cells, whereas it did so in PANC1 control cells. Taken together, these results indicate that the aberrant activation of the Hh signaling pathway is not common in colorectal cancer cell lines. © 2007 Wiley‐Liss, Inc.