Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas
| Autor: | John Varakis, Vasiliki Bravou, Stavroula G. Amanetopoulou, Helen Papadaki, Helen P. Kourea, Ioannis P. Gialmanidis |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Patched Receptors Pulmonary and Respiratory Medicine Cancer Research Pathology medicine.medical_specialty Lung Neoplasms Kruppel-Like Transcription Factors Gene Expression Receptors Cell Surface Zinc Finger Protein Gli2 Biology Zinc Finger Protein GLI1 Receptors G-Protein-Coupled GLI1 Carcinoma Non-Small-Cell Lung Parenchyma medicine Humans Hedgehog Proteins Hedgehog Aged Cell Proliferation Forkhead Box Protein M1 Nuclear Proteins Cancer Forkhead Transcription Factors Middle Aged medicine.disease Immunohistochemistry Smoothened Receptor Hedgehog signaling pathway respiratory tract diseases Patched-1 Receptor Oncology PTCH1 biology.protein Female Smoothened Signal Transduction Transcription Factors |
| Zdroj: | Lung Cancer. 66:64-74 |
| ISSN: | 0169-5002 |
| Popis: | The hedgehog (HH)-signaling pathway is implicated in developmental processes and its aberrant activation in adult tissues has been associated with malignancy. The aim of this study was to determine the expression pattern of HH-signaling molecules in non-small cell lung carcinomas (NSCLC), as well as the involvement of the transcription factor FOXM1, that controls cell proliferation, in this process. Paraffin-embedded tissue sections of 80 NSCLC cases and adjacent non-neoplastic lung parenchyma were immunohistochemically analyzed with anti-SHH, anti-Patched1 (PTCH1), anti-Smoothened (SMO), anti-GLI1, anti-GLI2 and anti-FOXM1 antibodies. Correlations of HH molecules with clinicopathological parameters and FOXM1 expression were evaluated. All the HH-signaling molecules examined were overexpressed in NSCLC compared with the adjacent non-neoplastic lung parenchyma. HH pathway activity and expression of PTCH1 and SMO were significantly higher in squamous cell carcinomas compared to other NSCLC histological types. Activation of HH pathway and PTCH1 expression were correlated with tumor grade being higher in low grade tumors. There was a significant correlation of lymph node metastases with expression of SMO in all NSCLC histological types and with nuclear GLI1 immunolocalization only in adenocarcinomas. Overexpression of FOXM1 in NSCLC was also significantly correlated with PTCH1, SMO and GLI1 expression. In conclusion, HH-signaling pathway is activated in NSCLC and correlates with histological type, prognostic parameters of the tumors as well as with the increased expression of FOXM1. |
| Databáze: | OpenAIRE |
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