AI Article Synopsis
- High doses of epidermal growth factor (EGF) can paradoxically trigger cell death (apoptosis) in A431 epidermoid carcinoma cells that overexpress EGF receptors, despite EGF being known to promote cell growth.
- The study reveals that the activation of the STAT1 transcription factor is vital for EGF-induced apoptosis in these cells.
- Researchers found that the p38 MAP kinase pathway is crucial in this process, as inhibiting it reduced both the growth-inhibiting and pro-apoptotic effects of EGF by decreasing the phosphorylation of STAT1, specifically on tyrosine 701.
Article Abstract
While epidermal growth factor (EGF) is a well known mitogen, high doses of EGF result in a paradoxical apoptotic response in the cells that overexpress EGF receptor such as A431 epidermoid carcinoma cells. EGF-induced apoptosis in A431 cells is dependent upon activation of transcription factor STAT1. In this study, we demonstrate that p38 MAP kinase is another important mediator of EGF-dependent pro-apoptotic response in A431 cells. By utilizing p38 MAP kinase inhibitors, SB203580 and BIRB0796, we significantly reduced the integral growth-inhibiting as well as pro-apoptotic effects of EGF. Moreover, we observed that inhibition of p38 MAP kinase markedly decreased phosphorylation of tyrosine 701 in STAT1, while neither EGF-induced accumulation nor serine phosphorylation of STAT1 was decreased. We propose that p38 MAP kinase mediates STAT1 tyrosine phosphorylation, thereby enforcing EGF-induced apoptosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2012.11.041 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!