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In Vitro and In Vivo effects of suppressor of cytokine signalling 7 knockdown in breast cancer: the influence on cellular response to hepatocyte growth factor

Sasi, Walid, Ye, Lin, Jiang, Wen Guo, Sharma, Anup K. and Mokbel, Kefah 2014. In Vitro and In Vivo effects of suppressor of cytokine signalling 7 knockdown in breast cancer: the influence on cellular response to hepatocyte growth factor. BioMed Research International 2014 , 648040. 10.1155/2014/648040

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Abstract

Purpose. 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. Methods. 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. Results. 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 . 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. Conclusions. 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Additional Information: © 2014 Walid Sasi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Hindawi Publishing Corporation
ISSN: 2314-6133
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 30 June 2014
Last Modified: 25 Mar 2019 16:44
URI: http://orca.cf.ac.uk/id/eprint/77446

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