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beta-Heregulin impairs EGF induced PLC-gamma 1 signalling in human breast cancer cells

机译:β-临床含量在人乳腺癌细胞中损害EGF诱导的PLC-GAMMA 1信号传导

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摘要

The interplay of ErbB receptor homo- and heterodimers plays a crucial role in the pathology of breast cancer since activated signal transduction cascades coordinate proliferation, survival and migration of cells. EGF and beta-Heregulin are well characterised ligands known to induce ErbB homo- and heterodimerisation, which have been associated with disease progression. In the present study, we investigated the impact of both factors on the migration of MDA-NEO and MDA-HER2 human breast cancer cells. MDA-NEO cells are positive for EGFR and HER3, while MDA-HER2 cells express EGFR, HER2 and HER3. Cell migration analysis revealed that beta-Heregulin potently impaired EGF induced migration in both cell lines. Western blot studies showed that both ErbB receptor and PLC-gamma 1 tyrosine phosphorylation levels were diminished in EGF and beta-Heregulin co-treated MDA-NEO and MDA-HER2 cells, which was further correlated to a significantly impaired calcium influx. Our data indicate that EGF and HRG may interfere with each other for receptor binding and dimerisation, which ultimately has an impact on signalling outcome.
机译:由于活性信号转导级联坐标,存活率和细胞迁移,ErbB受体同源和异二聚体的相互作用在乳腺癌的病理学中起着至关重要的作用。 EGF和β-β-尤其是已知的表征性配体,已知诱导ERBB均匀和异二聚体,其与疾病进展相关。在本研究中,我们研究了两种因素对MDA-Neo和MDA-HER2人乳​​腺癌细胞迁移的影响。 MDA-Neo细胞对于EGFR和HER3是阳性的,而MDA-HER2细胞表达EGFR,HER2和HER3。细胞迁移分析表明,β-临床蛋白在两种细胞系中诱导EGF诱导的迁移。 Western印迹研究表明,ERBB受体和PLC-GAMMA 1酪氨酸磷酸化水平在EGF和β-邻近蛋白共同处理的MDA-Neo和MDA-HER2细胞中减少,其与显着损害的钙流入钙化钙 - Her2细胞。我们的数据表明EGF和HRG可以彼此干扰受体结合和二聚化,这最终对信号结果产生了影响。

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