Signaling Pathway of GP88 (Progranulin) in Breast Cancer Cells: Upregulation and Phosphorylation of c-myc by GP88/Progranulin in Her2-Overexpressing Breast Cancer Cells.
Signaling Pathway of GP88 (Progranulin) in Breast Cancer Cells: Upregulation and Phosphorylation of c-myc by GP88/Progranulin in Her2-Overexpressing Breast Cancer Cells.
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乳腺癌细胞中GP88（预生素）的信号通路：通过GP88/PROGRANULIN在HER2过表达的乳腺癌细胞中，C-MYC上调和磷酸化。
DOI：
10.4137/bcbcr.s29371
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Serrero G
中科院分区：
文献类型：
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作者：
Kim WE;Yue B;Serrero G
Her 2是一种受体酪氨酸激酶，在25%的乳腺肿瘤中过表达。我们已经表明，88 kDa的自分泌生长和生存因子GP 88（颗粒蛋白前体）刺激Her 2磷酸化和增殖，并赋予Her 2过表达细胞的赫赛汀耐药性。在此，我们报告说，GP 88刺激c-myc磷酸化和上调c-myc在Her 2过表达细胞的水平。在非Her 2过表达乳腺癌细胞中未观察到c-myc磷酸化和GP 88上调。在用ERK、PI 3激酶和c-src通路抑制剂U 0126、LY 294002和PP 2处理后，c-myc活化被抑制。GP 88还刺激c-src磷酸化，这是一种已知的c-myc上游调节因子。因此，我们在此描述了GP 88在Her 2过表达细胞中的信号传导途径，GP 88刺激Src磷酸化，然后磷酸化和上调c-myc。这些数据表明，靶向GP 88可以为乳腺癌提供一种新的治疗方法。
Her2 is a receptor tyrosine kinase overexpressed in 25% of breast tumors. We have shown that the 88 kDa autocrine growth and survival factor GP88 (progranulin) stimulated Her2 phosphorylation and proliferation and conferred Herceptin resistance in Her2-overexpressing cells. Herein, we report that GP88 stimulates c-myc phosphorylation and upregulates c-myc levels in Her2-overexpressing cells. c-myc phosphorylation and upregulation by GP88 were not observed in non-Her2-overexpressing breast cancer cells. c-myc activation was inhibited upon treatment with ERK, PI3 kinase, and c-src pathway inhibitors, U0126, LY294002, and PP2. GP88 also stimulated c-src phosphorylation, a known upstream regulator of c-myc. Thus, we describe here a signaling pathway for GP88 in Her2-overexpressing cells, with GP88 stimulating Src phosphorylation, followed by phosphorylation and upregulation of c-myc. These data would suggest that targeting GP88 could provide a novel treatment approach in breast cancer.