Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas

World J Gastroenterol. 2007 Mar 21;13(11):1659-65. doi: 10.3748/wjg.v13.i11.1659.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / physiopathology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology*
  • Gene Expression Regulation, Neoplastic
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / physiology*
  • 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
  • Oncogene Proteins / physiology*
  • 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
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli3

Substances

  • Carrier Proteins
  • GLI3 protein, human
  • HHIP protein, human
  • Hedgehog Proteins
  • Keratins, Hair-Specific
  • Kruppel-Like Transcription Factors
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Oncogene Proteins
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • RNA, Messenger
  • Receptors, Cell Surface
  • SHH protein, human
  • Trans-Activators
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli3
  • Receptor, Platelet-Derived Growth Factor alpha