ABSTRACT
AIM: To determine the role of Sonic hedgehog (Shh) pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptch1, hedgehog-interacting protein (Hip), Gli1, Gli3 and PDGFRalpha. METHODS: Expression of Shh in 25 colorectal adeno-carcinomas was detected by RT-PCR, in situ hybridization and immunohistochemistry. Expression of Ptch1 was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Gli1, Gli3 and PDGFRalpha 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 Ptch1, Hip and Gli1 were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRalpha 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-Ptch1-Gli1 signaling pathway may play a role in the progression of colorectal tumor.
Subject(s)
Adenocarcinoma/physiopathology , Colorectal Neoplasms/physiopathology , Hedgehog Proteins/physiology , Oncogene Proteins/physiology , Signal Transduction/physiology , Trans-Activators/physiology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Carrier Proteins/genetics , Carrier Proteins/physiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Hedgehog Proteins/genetics , Humans , Keratins, Hair-Specific/genetics , Keratins, Hair-Specific/physiology , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/physiology , Membrane Glycoproteins/genetics , Membrane Glycoproteins/physiology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Oncogene Proteins/genetics , Patched Receptors , Patched-1 Receptor , RNA, Messenger/genetics , RNA, Messenger/physiology , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor alpha/physiology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/physiology , Trans-Activators/genetics , Zinc Finger Protein GLI1 , Zinc Finger Protein Gli3ABSTRACT
AIM: To study the expression of Sonic hedgehog pathway-related molecules, Sonic hedgehog (Shh) and Gli1 in gastric carcinoma. METHODS: Expression of Shh in 56 gastric specimens including non-cancerous gastric tissues, gastric adenocarcinoma, gastric squamous cell carcinoma was detected by RT-PCR, in situ hybridization and immunohistochemistry. Expression of Gli1 was observed by in situ hybridization. RESULTS: The positive rate of Shh and Gli1 expression was 0.0%, 0.0% in non-cancerous gastric tissues while it was 66.7%, 57.8% respectively in gastric adenocarcinoma, and 100%, 100% respectively in gastric squamous cell carcinoma. There was a significant difference between the non-cancerous gastric tissues and gastric carcinoma (P<0.05). Elevated expression of Shh and Gli1 in gastric tubular adenocarcinoma was associated with poorly differentiated tumors while the expression was absent in gastric mucinous adenocarcinoma. CONCLUSION: The elevated expression of Shh and Gli1 in gastric adenocarcinoma and gastric squamous cell carcinoma shows the involvement of activated Shh signaling in the cellular proliferation of gastric carcinogenesis. It suggests Shh signaling gene may be a new and good target gene for gastric tumor diagnosis and therapy.
