Gong Ni, Wu Runliu, Ding Boni, Wu Wei
Department of General Surgery, the Third Xiangya Hospital of Central South University, Changsha 410013, China.
Department of Thyroid and Breast Surgery, the Third Xiangya Hospital of Central South University, Changsha 410013, China.
Transl Cancer Res. 2020 May;9(5):3266-3273. doi: 10.21037/tcr-19-2132.
The regulatory roles of human epidermal growth factor receptor [erb-b2 receptor tyrosine kinase 4 (ERBB)] family in tumors was received widespread attention. Although ERBB4 was crucial regulator in metastasis of malignant tumors, the exact mechanism of ERBB4 in inflammatory breast cancer (IBC) remains unclarified.
In this study, we collected IBC tissues and cell lines, and explored the expression levels of ERBB4 and platelet-derived growth factor receptor alpha (PDGFRA) using real-time quantitative polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blot assays. Furthermore, cell viability with ERBB4 silencing in SUM149 cells was examined by MTT assay and cell migration and invasion were detected by transwell assay.
The data indicated thatERBB4abolishing dramatically depressed capacity of proliferation, migration and invasion of IBC cells. Moreover, PDGFRA was an important factor for the function of ERBB4 and PDGFRA overexpression could, at least, partly rescue the ERBB4 silencing-mediated inhibition in proliferation and metastasis of IBC cells.
Take together, we verified the first time that ERBB4 promoted the progression of IBC through regulating PDGFRA. Thus, inhibition of ERBB4 might be a novel therapeutic candidate against IBC.
人类表皮生长因子受体[erb-b2受体酪氨酸激酶4（ERBB）]家族在肿瘤中的调控作用受到广泛关注。尽管ERBB4是恶性肿瘤转移的关键调节因子，但其在炎性乳腺癌（IBC）中的具体机制仍不清楚。
在本研究中，我们收集了IBC组织和细胞系，采用实时定量聚合酶链反应（RT-PCR）、免疫组织化学（IHC）和蛋白质免疫印迹法检测ERBB4和血小板衍生生长因子受体α（PDGFRA）的表达水平。此外，通过MTT法检测SUM149细胞中ERBB4沉默后的细胞活力，并通过Transwell法检测细胞迁移和侵袭能力。
数据表明，ERBB4缺失显著降低了IBC细胞的增殖、迁移和侵袭能力。此外，PDGFRA是ERBB4功能的重要因素，PDGFRA过表达至少可以部分挽救ERBB4沉默介导的对IBC细胞增殖和转移的抑制作用。
综上所述，我们首次证实ERBB4通过调节PDGFRA促进IBC的进展。因此，抑制ERBB4可能是一种针对IBC的新型治疗候选方法。
