| Autor: |
Huang, Lieven, Verstrepen, L, Heyninck, K, Wullaert, Andy, Revets, Hilde, De Baetselier, Patrick, Beyaert, R. |
| Přispěvatelé: |
Cellular and Molecular Immunology |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
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| Popis: |
The epidermal growth factor receptor (EGFR) is frequently overexpressed in various tumours of epidermal origin and is held responsible for tumourigenicity and tumour persistence. Increased nuclear factor (NF)-kappaB activity has been suggested to be involved in the malignant behaviour of EGFR-overexpressing cells. However, the mechanisms that regulate EGF-induced NF-kappaB activation are still largely unknown. Here we show that EGF can inducuce NF-kappaB-dependent gene expression independently from I kappa B alpha degradation or p100 processing in EGFR-overexpressing HEK293T cells. Moreover, EGF-induced NF-kappaB activation could be inhibited by overexpression of ABINs, which were previously identified as intracellular inhibitors of tumour necrosis factor, interleukin-1 and lypopolysaccharide-induced NF-kappaB activation. Knockdown of ABIN1 by RNA interference boosted the NF-kappaB response upon EGF stimulation. The C-terminal ubiquitin-binding domain containing region of ABINs was cruvial and sufficient for NF-kappaB inhibition. Adenoviral gene transfer of ABINs reduced constitutive NF-kappaB activity as well as the proliferation of EGFR-overexpressing A431 and DU145 human carcinoma cells. Altogether, these results demonstrate an important role for an ABIN-sensitive non-classical NF-kappaB signalling pathway in the prolilferation of EGFR-overexpressing tumour cells, and indicate a potential use for ABIN gene therapy in the treatment of cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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