Phosphorylation of both EGFR and ErbB2 is a reliable predictor of prostate cancer cell proliferation in response to EGF
Phosphorylation of both EGFR and ErbB2 is a reliable predictor of prostate cancer cell proliferation in response to EGF
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DOI：
10.1593/neo.04379
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发表时间：
2004-11-01
期刊：
影响因子：
4.8
通讯作者：
Lalani, EN
中科院分区：
文献类型：
--
作者：
El Sheikh, SS;Domin, J;Lalani, EN
尽管有多个关于前列腺癌 (PC) 中过度表达的报道，但 PC 细胞对激活的表皮生长因子受体 (EGFR) 及其下游磷酸肌醇 3'-激酶/Akt (PI3K/Akt/PTEN) 和/或丝裂原激活蛋白激酶 (MAPK/ERK) 通路的依赖尚未完全阐明。在本研究中，我们比较了 EGF 介导的信号传导在非恶性（BPH-1、PNT1A 和 PNT1B）和 PC 细胞系（DU145、PC3、LNCaP 和 CWR22Rv1）中的作用。在除 PC3 之外的所有表达 EGFR 的 PC 细胞中均观察到 EGF 诱导的增殖，表明 EGFR 表达在 EGF 刺激后并未明确触发增殖。尽管 EGFR 表达较低，但 ErbB2 的募集增强了 EGF 诱导的信号，并且与 EGF 最显着的作用相关。通过这种方式，EGFR 和 ErbB2 受体磷酸化的总和被证明是比单独量化任一受体表达更敏感的 EGF 诱导增殖指标。 Akt 和 ERK 均响应 EGF 快速磷酸化，其中 ERK 磷酸化在 PC3 细胞中最弱。将这些发现外推到临床 PC 表明，磷酸化 EGFR + ErbB2 一起评估可以作为抗 EGFR 靶向治疗敏感性的标志物。
Despite multiple reports of overexpression in prostate cancer (PC), the reliance of PC cells on activated epidermal growth factor receptor (EGFR) and its downstream signaling to phosphoinositide 3'-kinase/Akt (PI3K/Akt/PTEN) and/or mitogen-activated protein kinase (MAPK/ERK) pathways has not been fully elucidated. In this study, we compared the role of EGF-mediated signaling in nonmalignant (BPH-1, PNT1A, and PNT1B) and PC cell lines (DU145, PC3, LNCaP, and CWR22Rv1). EGF-induced proliferation was observed in all EGFR-expressing PC cells except PC3, indicating that EGFR expression does not unequivocally trigger proliferation following EGF stimulation. ErbB2 recruitment potentiated EGF-induced signals and was associated with the most pronounced effects of EGF despite low EGFR expression. In this way, the sum of EGFR and ErbB2 receptor phosphorylation proved to be a more sensitive indicator of EGF-induced proliferation than quantification of the expression of either receptor alone. Both Akt and ERK were rapidly phosphorylated in response to EGF, with ERK phosphorylation being weakest in PC3 cells. Extrapolation of these findings to clinical PC suggests that assessment of phosphorylated EGFR + ErbB2 together could serve as a marker for sensitivity to anti-EGFR-targeted therapies.