EGF-induced apoptosis in A431 cells is dependent on STAT1, but not on STAT3
EGF-induced apoptosis in A431 cells is dependent on STAT1, but not on STAT3
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DOI：
10.1016/j.ejcb.2007.05.009
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发表时间：
2007-10-01
影响因子：
6.6
通讯作者：
Nikolsky, Nikolay N.
中科院分区：
文献类型：
--
作者：
Grudinkin, Pavel S.;Zenin, Valery V.;Nikolsky, Nikolay N.
高浓度的表皮生长因子（EGF）对人表皮样癌细胞A431具有生长抑制作用。转录因子STAT1是介导这种作用的最可能的候选因子。在本研究中，我们发现A431细胞的EGF抗性亚克隆中STAT1的表达水平显著降低。引入野生型STAT1可逆转EGF抗性，但引入其Y701F突变体则不能。此外，阻断Src家族激酶的活性可降低STAT1和STAT3的酪氨酸磷酸化，并保护A431细胞免受EGF诱导的生长抑制。为了进一步阐明STATs在A431细胞生长和存活中的作用，我们构建了针对STAT1或STAT3表达短发夹RNA（shRNA）的A431细胞克隆。在没有EGF的情况下，STAT1或STAT3的敲低对A431细胞的生长速率或凋亡死亡均无任何影响。然而，在EGF处理后，与A431细胞相比，STAT1被敲低的A431细胞继续生长，且凋亡水平显著降低。STAT3的敲低不改变细胞生长或凋亡。综上所述，我们的实验证明了酪氨酸磷酸化的STAT1（而非STAT3）在EGF诱导的A431细胞凋亡中起关键作用。（C）2007爱思唯尔股份有限公司。保留所有权利。
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. (C) 2007 Elsevier GmbH. All rights reserved.