AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, ...AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.展开更多
The Hedgehog(Hh)family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers.To ensure the proper range of signaling,t...The Hedgehog(Hh)family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers.To ensure the proper range of signaling,the Hh proteins are modified with lipids,assembled into water-soluble multimers,and interact with multiple cell surface proteins.In the target cells,a largely conserved intracellular signal transduction pathway,from the cell surface receptor Patched to the Glioma-associated oncogene homolog(Gli)family of transcription factors,mediates the transcriptional responses from fruit flies to mammals.A significant divergence between vertebrates and insects is the vertebrate-specific requirement of cilia for Hh signal transduction and Gli protein activation.Finally,transcription-independent cellular responses to Hh have been described in certain developmental processes.With clinical trial underway to treat Hhrelated diseases,more work is urgently needed to reach a more comprehensive understanding of the molecular mechanisms underlying the regulation of Hh signaling in development and diseases.展开更多
基金grants from National Natural Science Foundation of China, No. 30228031, No. 30671072
文摘AIM： To determine the role of Sonic hedgehog （Shh） pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein （Hip）, Gil1, Gli3 and PDGFRα. METHODS： Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR,in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gil1, Gli3 and PDGFRα was analyzed by in situ hybridization. RESULTS： Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Gill were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRα was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas. CONCLUSION： These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.
文摘The Hedgehog(Hh)family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers.To ensure the proper range of signaling,the Hh proteins are modified with lipids,assembled into water-soluble multimers,and interact with multiple cell surface proteins.In the target cells,a largely conserved intracellular signal transduction pathway,from the cell surface receptor Patched to the Glioma-associated oncogene homolog(Gli)family of transcription factors,mediates the transcriptional responses from fruit flies to mammals.A significant divergence between vertebrates and insects is the vertebrate-specific requirement of cilia for Hh signal transduction and Gli protein activation.Finally,transcription-independent cellular responses to Hh have been described in certain developmental processes.With clinical trial underway to treat Hhrelated diseases,more work is urgently needed to reach a more comprehensive understanding of the molecular mechanisms underlying the regulation of Hh signaling in development and diseases.
