Sasi Walid, Ye Lin, Jiang Wen G, Sharma Anup K, Mokbel Kefah
St. George's University of London, London SW17 0RE, UK.
Cardiff University, Cardiff CF10 3XQ, UK.
Biomed Res Int. 2014;2014:648040. doi: 10.1155/2014/648040. Epub 2014 Aug 4.
Suppressor of cytokine signaling 7 (SOCS7) is a member of the SOCS family and is known to interact with phospholipase Cγ-1 (PLCγ-1), a key downstream mediator of the hepatocyte growth factor (HGF)/C-MET axis. Here, we report our observations of the effect of knocking down SOCS7 gene on the behaviour of breast cancer cells both in vitro and in vivo and to elucidate whether this involves HGF/C-MET pathway using the PLCγ-1 blocker U73122.
MCF7 and MDA-MB-231 breast cancer cells were transfected with anti-SOCS7 ribozymal transgene, to create sublines with SOCS7 knockdown. The in vitro growth and migration of the cells were evaluated in basic conditions and with HGF and U73122 treatment using growth assays, scratch-wound, and electrical cell impedance sensing (ECIS) migration assays. MCF7 and MDA-MB-231 in vivo tumour xenograft growth were also studied.
Basal in vitro growth and migration of both cellular lines and the in vivo MCF7 xenograft growth were significantly enhanced with SOCS7 knockdown. In vitro HGF treatment has further influenced the growth and migration when SOCS7 gene was knocked-down in both cellular lines (P < 0.05). PLCγ-1 pharmacological inhibition of the HGF/C-MET cascade during their in vitro growth and migration seemed to only occur when SOCS7 gene was knocked down.
We report a unique regulatory role for SOCS7 in controlling the malignant behaviour of breast cancer lines MCF7 and MDA-MB-231 in vitro and the MCF7 tumour xenografts in vivo. We also report a regulatory role for SOCS7 during the in vitro HGF-induced growth and migration in these cells as HGF treatment and SOCS7 loss have synergistically enhanced these functions. This SOCS7 knockdown-attributed effect could be due to a precise anti-PLCγ-1 role.
细胞因子信号转导抑制因子7（SOCS7）是SOCS家族的成员，已知其与磷脂酶Cγ-1（PLCγ-1）相互作用，磷脂酶Cγ-1是肝细胞生长因子（HGF）/C-MET轴的关键下游介质。在此，我们报告了敲低SOCS7基因对乳腺癌细胞体外和体内行为的影响的观察结果，并使用PLCγ-1阻滞剂U73122阐明这是否涉及HGF/C-MET途径。
用抗SOCS7核酶转基因转染MCF7和MDA-MB-231乳腺癌细胞，以创建敲低SOCS7的亚系。使用生长测定、划痕损伤和电场细胞阻抗传感（ECIS）迁移测定，在基础条件下以及HGF和U73122处理下评估细胞的体外生长和迁移。还研究了MCF7和MDA-MB-231在体内肿瘤异种移植的生长情况。
敲低SOCS7后，两种细胞系的基础体外生长和迁移以及体内MCF7异种移植的生长均显著增强。当两个细胞系中的SOCS7基因被敲低时，体外HGF处理进一步影响了生长和迁移（P < 0.05）。在体外生长和迁移过程中，PLCγ-1对HGF/C-MET级联的药理抑制似乎仅在SOCS7基因被敲低时发生。
我们报告了SOCS7在体外控制乳腺癌细胞系MCF7和MDA-MB-231以及体内MCF7肿瘤异种移植的恶性行为中的独特调节作用。我们还报告了SOCS7在这些细胞体外HGF诱导的生长和迁移过程中的调节作用，因为HGF处理和SOCS7缺失协同增强了这些功能。这种敲低SOCS7引起的效应可能归因于精确的抗PLCγ-1作用。
