title: Gli2 protein expression level is a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms.
abstract: The hedgehog pathway is known to promote proliferation of pancreatic ductal adenocarcinoma (PDA) and has been shown to restrain tumor progression. To understand how hedgehog causes these effects, we sought to carefully examine protein expression of hedgehog signaling components during different tumor stages. Genetically engineered mice, Pdx1-Cre;LSL-KrasG12D and Pdx1-Cre;LSL-KrasG12D;p53lox/+, were utilized to model distinct phases of tumorigenesis, pancreatic intraepithelial neoplasm (PanIN) and PDA. Human pancreatic specimens of intraductal papillary mucinous neoplasm (IPMN) and PDA were also employed. PanIN and IPMN lesions highly express Sonic Hedgehog, at a level that is slightly higher than that observed in PDA. GLI2 protein is also expressed in both PanIN/IPMN and PDA. Although there was no difference in the nuclear staining, the cytoplasmic GLI2 level in PDA was modest in comparison to that in PanIN/IPMN. Hedgehog interacting protein was strongly expressed in the precursors, whereas the level in PDA was significantly attenuated. There were no differences in expression of Patched1 at early and late stages. Finally, a strong correlation between Sonic Hedgehog and GLI2 staining was found in both human and murine pancreatic tumors. The results indicate that the GLI2 protein level could serve as a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Junpei Sasajima, MD, PhD, Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510, Japan, tel. +81-166682462, fax +81-166682469, e-mail: junsasaji@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Sasajima
authors.forename: Y
authors.initials: Y
authors.lastname: Mizukami
authors.forename: K
authors.initials: K
authors.lastname: Koizumi
authors.forename: T
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ono
authors.forename: H
authors.initials: H
authors.lastname: Karasaki
authors.forename: H
authors.initials: H
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Fujiya
authors.forename: Y
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D008024:Ligands; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000075746:Zinc Finger Protein Gli2
chemical_list: D014408:Biomarkers, Tumor; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008024:Ligands; D000075746:Zinc Finger Protein Gli2