Identification of a functional EGF-R/p60c-src/STAT3 pathway in colorectal carcinoma: Analysis of its long-term prognostic value
| Autor: | Christine Lagorce, Olivier Rixe, Antoine Martin, A. Tadlaoui Hbibi, J-P. Spano, Remi Fagard, Jean-Luc Breau, Robert Benamouzig, G. Des Guetz, G. Milano, Philippe Wind, J.-F. Morere |
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| Rok vydání: | 2008 |
| Předmět: |
STAT3 Transcription Factor
Cancer Research Pathology medicine.medical_specialty Colorectal cancer Proto-Oncogene Proteins pp60(c-src) Perineural invasion Genetics medicine Humans Phosphorylation Tyrosine STAT3 Aged Neoplasm Staging biology General Medicine Prognosis medicine.disease Immunohistochemistry ErbB Receptors Oncology Tissue Array Analysis biology.protein Cancer research Colorectal Neoplasms Tyrosine kinase Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1875-8592 1574-0153 |
| DOI: | 10.3233/cbm-2008-4204 |
| Popis: | Aims: The Epidermal Growth Factor-Receptor (EGF-R) is frequently overexpressed in colorectal carcinoma (CRC) and patients can benefit from anti-EGF-R therapy. Yet, the relationship, within tumours, between EGF-R and the activity of downstream effectors such as the non-receptor tyrosine kinase p60c-src and the signal transducer and activator of transcription 3 (STAT3) has not been extensively analyzed. Methods and results: We evaluated EGF-R, tyrosine 416-phosphorylated p60c-src (P-p60c-src), STAT3 and tyrosine 705- phosphorylated STAT3 (P-STAT3) on Tissue Micro Array (TMA) from 126 patients with CRC. Composite immunohistochemistry scores based on the intensity of labelling and the percentage of positive cells were determined on TMA for EGF-R, P-p60c-src, STAT3 and P- STAT3. A high score was found in 56%, 61%, 62% and 27% of the cases for EGF-R, P-p60c-src, STAT3 and P-STAT3 respectively. There was a significant correlation between EGF-R and P-p60c-src (p =0 .006) and between P-p60c-src and P-STAT3 (p =0 .0009). STAT3 was significantly correlated with vascular emboli ( p =0 .03) and perineural invasion (p =0 .02). Conclusions: The correlations between EGF-R, P-p60-src and P-STAT3 and some stage-related pathological features point to a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within CRC tumours. |
| Databáze: | OpenAIRE |
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