EGF-induced apoptosis in A431 cells is dependent on STAT1, but not on STAT3
| Autor: | Nikolay Nikolsky, Andrey V. Kropotov, Viktoria N. Dorosh, V. V. Zenin, Pavel S. Grudinkin |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
STAT3 Transcription Factor
Histology Apoptosis DNA Fragmentation macromolecular substances Pathology and Forensic Medicine Small hairpin RNA chemistry.chemical_compound Epidermal growth factor Cell Line Tumor Humans Phosphorylation RNA Small Interfering skin and connective tissue diseases STAT3 neoplasms Electrophoresis Agar Gel Epidermal Growth Factor biology Cell growth Tyrosine phosphorylation Cell Biology General Medicine Molecular biology STAT1 Transcription Factor src-Family Kinases Epidermoid carcinoma chemistry Cell culture Carcinoma Squamous Cell biology.protein Tyrosine biological phenomena cell phenomena and immunity A431 cells hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | European Journal of Cell Biology. 86:591-603 |
| ISSN: | 0171-9335 |
| DOI: | 10.1016/j.ejcb.2007.05.009 |
| Popis: | EGF in high concentrations has a growth-inhibitory effect on human epidermoid carcinoma cells A431. The transcription factor STAT1 is the most probable candidate for mediating this effect. In the present study, we demonstrated a strong reduction of the expression level of STAT1 in EGF-resistant sub-clones of A431 cells. EGF resistance was reversed by introducing wild-type STAT1, but not its Y701F mutant. Moreover, blocking the activity of Src family kinases reduced tyrosine phosphorylation of STAT1 and STAT3 and protected A431 cells from the EGF-induced growth inhibition. To further elucidate roles of STATs in A431 cell growth and survival, clones of A431 cells expressing short hairpin RNA (shRNA) against STAT1 or STAT3 were generated. Neither STAT1 nor STAT3 knockdown exerted any effect on growth rate or apoptotic death of A431 cells in the absence of EGF. However, upon EGF treatment A431 cells with knocked down STAT1 continued to grow and demonstrated a significantly lower level of apoptosis as compared to A431 cells. The knockdown of STAT3 did not alter cell growth or apoptosis. Taken together, our experiments prove the essential role of tyrosine phosphorylated STAT1, but not of STAT3, in EGF-induced apoptosis in A431 cells. |
| Databáze: | OpenAIRE |
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