Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells
| Autor: | Daniele Fina, R Caruso, E Calabrese, Roberto Testi, I Monteleone, S. Bellinvia, F Pallone, L Franchi, G. Monteleone, P. Vavassori, G.C. Naccari |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Apoptosis Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein tyrosine phosphatase Non-Receptor Type 6 RNA interference Epidermal growth factor receptor Phosphorylation RNA Small Interfering Mesalamine Settore MED/12 - Gastroenterologia Gene knockdown Tumor Blotting Protein Tyrosine Phosphatase Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins ErbB Receptors Gene Expression Regulation Neoplastic surgical procedures operative Receptor Epidermal Growth Factor Enzyme Activation Humans Immunoprecipitation Cell Line Tumor Cell Proliferation Protein Tyrosine Phosphatases Blotting Western RNA Interference Adenocarcinoma Colorectal Neoplasms Western Receptor Biology Small Interfering Non-Receptor Type 11 Cell Line Dephosphorylation Gene silencing Molecular Biology Neoplastic Epidermal Growth Factor Cell Biology digestive system diseases Gene Expression Regulation Cell culture Immunology Cancer research biology.protein RNA Protein Tyrosine Phosphatase |
| Zdroj: | Cell death and differentiation. 13(2) |
| ISSN: | 1350-9047 |
| Popis: | Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth. |
| Databáze: | OpenAIRE |
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