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 β-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 β-Heregulin potently impaired EGF induced migration in both cell lines. Western blot studies showed that both ErbB receptor and PLC-γ1 tyrosine phosphorylation levels were diminished in EGF and β-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.

ErbB受体同二聚体和异二聚体的相互作用在乳腺癌的病理中起着至关重要的作用，因为激活的信号转导级联反应可协调细胞的增殖，存活和迁移。EGF和β-Heregulin是已知可诱导ErbB均二聚和异二聚化的良好表征的配体，与疾病进展相关。在本研究中，我们调查了这两种因素对MDA-NEO和MDA-HER2人乳​​腺癌细胞迁移的影响。MDA-NEO细胞对EGFR和HER3呈阳性，而MDA-HER2细胞表达EGFR，HER2和HER3。细胞迁移分析表明，β-Heregulin强烈削弱了EGF诱导的两种细胞系的迁移。蛋白质印迹研究表明，EGF和β-Heregulin共同处理的MDA-NEO和MDA-HER2细胞中，ErbB受体和PLC-γ1酪氨酸的磷酸化水平均降低，这与钙流入明显受损有关。我们的数据表明EGF和HRG可能在受体结合和二聚化方面相互干扰，最终对信号转导产生影响。