EGFR and her-2 regulate the constitutive activation of NF-KappaB in PC-3 prostate cancer cells
EGFR and her-2 regulate the constitutive activation of NF-KappaB in PC-3 prostate cancer cells
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DOI：
10.1002/pros.20234
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发表时间：
2005-10-01
期刊：
影响因子：
2.8
通讯作者：
Saad, F
中科院分区：
文献类型：
--
作者：
Le Page, C;Koumakpayi, IH;Saad, F
背景。 NF-kappaB (NF-kappa B) 在前列腺癌细胞中持续激活的机制仍不清楚。我们研究了表皮生长因子受体 (EGFR) ErbB 家族的成员是否参与前列腺癌细胞系中 NF-κ B 的组成型激活。方法和结果。 EGFR、Her-2 和 ErbB3 在 PC-3、DU145 和 LNCaP 前列腺癌细胞系中表达并组成型激活。使用几种药理学 ErbB 抑制剂，我们证明 EGFR 和 Her-2 通过两种不同的机制参与 PC-3 细胞中 NF-κ B 的组成型激活。 EGFR 通过丝氨酸 32/36 上 I kappa B α 的磷酸化激活 NF-kappa B，从而影响 p65 亚基的核转位。相反，Her-2 独立于丝氨酸 32/36 上的 I kappa B α 磷酸化而激活 NF-kappa B。 结论。这项研究直接表明 ErbB 受体参与 PC-3 前列腺癌细胞中 NF-kappa B 的激活。
BACKGROUND. The mechanism through which NF-kappaB (NF-kappa B) is constitutively activated in prostate cancer cells remains unclear. We investigated whether members of the ErbB family of epidermal growth factor receptors (EGFR) are involved in the constitutive activation of NF-kappa B in prostate cancer cell lines.METHODS AND RESULTS. EGFR, Her-2, and ErbB3 are expressed and constitutively activated in PC-3, DU145, and LNCaP prostate cancer cells lines. Using several pharmacological ErbB inhibitors, we demonstrate that EGFR and Her-2 are involved in the constitutive activation of NF-kappa B in PC-3 cells through two different mechanisms. EGFR activates NF-kappa B through the phosphorylation of I kappa B alpha on serines 32/36 thereby influencing the nuclear translocation of the p65 subunit. In contrast, Her-2 activates NF-kappa B independently of I kappa B alpha phosphorylation on serines 32/36.CONCLUSION. This study directly implicates ErbB receptors in the activation of NF-kappa B in PC-3 prostate cancer cells.