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Heregulin activates IKK/NF-κB signal pathway via Her2 in SKBR3 cell lines

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

2017 04
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Heregulin activates IKK/NF-κB signal pathway via Her2 in SKBR3 cell lines
Jin BoQiu HuilingLi Yuping
Department of Gynecology,the No.174 Hospital of the Chinese People's Liberation Army,the Chenggong Hospital Affiliated to Xiamen University,Fujian Xiamen 361001,China.
Objective:To study the activation mechanism of IKK/NF-κB signaling pathway which induced by Her2 agonist Heregulin (HRG) in human breast cancer SKBR3 cells.Methods:Western blotting method was used to detect the effect of HRG on PI3K/Akt/IKK signaling pathway in SKBR3 cells.Taken the classic signal pathway TNF-α/RIP1/IKK as a control,the inhibitors of key protein (PI3K,RIP1 and IKK)in various pathways were introduced to study the relationship between IKK/NF-κB and HRG.The effect of HRG on the proliferation of SKBR3 cells and the antagonistic effect of IKK inhibitor TPCA1 on HRG were monitored by real time non labeled cell analysis technique.Results:Both HRG and TNF-α could promote NF-κB into the nucleus by activating IKK.RIP1 inhibitor Necrostatin-1 could block the activation of IKK which induced by TNF-α,but was invalid for HRG,which indicated that HRG was able to activate IKK via non-traditional pathways.The activation of IKK which activated by HRG could be blocked by PI3K inhibitor LY294002,in addition,PI3K was one of primary proteins in Her2 pathway,so,we speculated that HRG could activate IKK/NF-κB pathway via the PI3K/Akt signaling pathway.The cell growth curve showed that HRG could promote the proliferation of SKBR3 cells and TPCA1 was able to reserve its effect,when treated with 100nmol/L TPCA1 in logarithmic phase,and the proliferation rate of SKBR3 cells decreased rapidly.Conclusion:HRG can promote the activation of NF-κB signaling pathway in SKBR3 cells through the Her2/PI3K/Akt pathway.


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