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首页> 外文期刊>Cellular Signalling >Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: Agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cells
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Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: Agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cells

机译：生长抑素受体1和5与表皮生长因子受体异源二聚体：乳腺癌细胞下游MAPK信号通路的激动剂依赖性调节

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The role of somatostatin (SST) and epidermal growth factor (EGF) in breast cancer is undisputed: however, the molecular mechanisms underlying their antiproliferative or proliferative effects are not well understood. We initially confirmed that breast turnout tissues express all five somatostatin receptors (SSTR1-5) and four epidermal growth factor receptors (ErbB1-4). Subsequently, to gain insight into the function of SSTRs and ErbBs in oestrogen receptor (ER)-positive (MCF-7) or ER alpha-negative (MDA-MB-231) breast cancer cells, we defined SSTR1, SSTR5 and ErbB1 mRNA and protein expression in these two tumour cell lines. Consistent with previous studies showing SSTR1/SSTR5 heterodimerization and having seen cell-specific and ligand-selective alterations in receptor expression, we next elucidated whether SSTR1 and SSTR5 functionally interactwith ErbB1 using pbFRET analysis. We subsequently determined the effects of SST and EGF either alone, or in combination, on selected downstream signalling molecules such as erk1/2, p38 and JNK. Here, we showed that both SST and EGF influenced erk1/2 phosphorylation and that SST modulated the effects of EGF in a cell-specific manner. We also demonstrated agonist-, time and cell-dependent regulation of p38 phosphorylation. We further investigated modulation of Grb2, SOS, Shc, SH-PTP1 and SH-PTP2. ErbB1 adaptor proteins known to play a role in MAPK activation, Shc, Grb2 and SOS, changed in an agonist- and cell-specific manner whereas, SH-PTP1 and SH-PTP2, adaptor proteins reported to interact with SSTRs, translocated from the cytosol to membrane in a cell-specific manner following SST and/or EGF treatment. Although several previous studies have shown crosstalk between RTKs and GPCRs, there are no reports describing SSTR (GPCR) modulation of ErbBs (RTK) in breast cancer. To the best of our knowledge, this is the first report describing crosstalk/interactions between SSTRs and ErbBs. (c) 2008 Published by Elsevier Inc.
机译：生长抑素（SST）和表皮生长因子（EGF）在乳腺癌中的作用是无可争议的;但是，它们的抗增殖或增生作用的分子机制尚不清楚。我们最初确认，乳房道岔组织表达所有五个生长抑素受体（SSTR1-5）和四个表皮生长因子受体（ErbB1-4）。随后，为了深入了解SSTR和ErbB在雌激素受体（ER）阳性（MCF-7）或ERα阴性（MDA-MB-231）乳腺癌细胞中的功能，我们定义了SSTR1，SSTR5和ErbB1 mRNA和蛋白在这两个肿瘤细胞系中的表达。与先前的研究显示SSTR1 / SSTR5异二聚化并已观察到受体表达中的细胞特异性和配体选择性变化相一致，我们接下来使用pbFRET分析阐明了SSTR1和SSTR5是否与ErbB1功能相互作用。我们随后确定了SST和EGF单独或组合对选定的下游信号传导分子（如erk1 / 2，p38和JNK）的影响。在这里，我们表明SST和EGF都影响erk1 / 2磷酸化，并且SST以细胞特异性方式调节EGF的作用。我们还证明了p38磷酸化的激动剂，时间和细胞依赖性调节。我们进一步研究了Grb2，SOS，Shc，SH-PTP1和SH-PTP2的调制。已知在激动剂和细胞特异性方式中，ErbB1衔接子蛋白在MAPK激活，Shc，Grb2和SOS中起作用，而SH-PTP1和SH-PTP2介导与SSTR相互作用的衔接子蛋白从细胞质中转移在SST和/或EGF处理后，以细胞特异性方式介导膜。尽管先前的一些研究表明RTK与GPCR之间存在串扰，但尚无报道描述乳腺癌中ErbBs（RTK）的SSTR（GPCR）调节。据我们所知，这是第一个描述SSTR和ErbB之间的串扰/相互作用的报告。 （c）2008年，Elsevier Inc.发行。

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