Sex-steroid hormones and EGF signalling in breast and prostate cancer cells: Targeting the association of Src with steroid receptors
Sex-steroid hormones and EGF signalling in breast and prostate cancer cells: Targeting the association of Src with steroid receptors
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DOI：
10.1016/j.steroids.2008.01.023
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发表时间：
2008-10-01
期刊：
影响因子：
2.7
通讯作者：
Castoria, Gabriella
中科院分区：
文献类型：
--
作者：
Auricchio, Ferdinando;Migliaccio, Antimo;Castoria, Gabriella
性类固醇激素触发其受体与信号效应器的关联。值得注意的是，这种关联会引发各种激素效应，例如不同细胞类型的 DNA 合成。在乳腺癌和前列腺癌细胞中，EGF、雄激素或雌二醇触发 AR/ER/Src 复合物的组装。 SH2-Src 与 ER 的磷酸酪氨酸残基相互作用，SH3-Src 与 AR 富含脯氨酸的序列相互作用。这种关联刺激 Src 依赖性信号传导、DNA 合成和细胞骨架变化。我们现在报道，在 EGF 或雄激素或雌二醇刺激的前列腺或乳腺癌细胞中，源自 ER 或 AR 序列的小肽（6-10 个氨基酸）参与受体与 Src 的相互作用，阻止 AR/ER/Src 关联、Src/Erk 通路刺激、细胞周期蛋白 D1 表达和 DNA 合成。肽的作用仅限于表达类固醇受体的细胞以及由这些受体介导的信号。值得注意的是，这些肽不会改变类固醇受体依赖性转录活性。这些新型受体拮抗剂强烈抑制前列腺或乳腺癌细胞异种移植物的生长。 (C) 2008 Elsevier Inc. 保留所有权利。
Sex-steroid hormones trigger association of their receptors with signalling effectors. Remarkably, various hormonal effects, such as DNA synthesis of different cell types are evoked by this association. In mammary and prostate cancer cells, EGF, androgen or estradiol trigger the assembly of AR/ER/Src complex. SH2-Src interacts with a phosphotyrosine residue of ER and SH3-Src interacts with a proline rich sequence of AR. This association stimulates Src-dependent signalling, DNA synthesis and cytoskeleton changes. We now report that in prostate or breast cancer cells stimulated by EGF or androgen or estradiol, small peptides (6-10 amino acids) derived from ER or AR sequences involved in the receptor interaction with Src, prevent AR/ER/Src association, Src/Erk pathway stimulation, cyclin D1 expression and DNA synthesis. The peptide action is restricted to cells expressing the steroid receptors and to signals mediated by these receptors. Remarkably, the peptides do not modify the steroid receptor-dependent transcriptional activity. Growth of prostate or mammary cancer cell xenografts is strongly inhibited by these novel receptor antagonists. (C) 2008 Elsevier Inc. All rights reserved.