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Observations on the effects of Suppressor of Cytokine Signaling 7 (SOCS7) knockdown in breast cancer cells: their in vitro response to Insulin Like Growth Factor I (IGF-I)

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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), one of the insulin-like growth factor-I (IGF-I) receptor downstream molecules. In this study, we sought to observe the effect of knocking down SOCS7 gene on breast cancer cells in vitro growth and migration and to elucidate whether this involves IGF-I-PLCγ1 route using the PLCγ-1 blocker U73122.

Methods

Suitable breast cancer cells (MCF7 and MDA-MB-231) were transfected with anti-SOCS7 ribozymal transgene, to create sub-lines with SOCS7 knockdown verified by RT-PCR. The growth and migration of the cells were evaluated in the presence or absence of IGF-I and PLCγ-1 inhibitor using growth assay, scratch-wound and electrical cell impedance sensing (ECIS) migration assays.

Results

IGF-I treatment produced more pronounced influence on MCF7 growth and migration and on MDA-MB-231 migration when SOCS7 gene was knocked down in both lines (p < 0.05). The absence of IGF-I-induced growth response in MDA-MB-231 could be due to the intrinsic characteristics of these cells. PLCγ-1 pharmacological inhibition during their in vitro migration seemed to only occur when SOCS7 gene was knocked down.

Conclusions

To the best of our knowledge, this is the first report of the SOCS7 regulatory role in IGF-I induced in vitro functions in ER-positive and ER-negative breast cancer cells. IGF-I treatment and SOCS7 loss have synergistically resulted in increased growth and migration of MCF7 and in increased migration of MDA-MB-231 cells. The migratory effects could be due to a precise anti-PLCγ-1 role.

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Authors and Affiliations

  1. St George’s, University of London, Cranmer Terrace, London, SW17 0RE, UK

    W. Sasi, K. Mokbel & A. Sharma

  2. Cardiff University, Cardiff, Wales, UK

    L. Ye & W. G. Jiang

  3. The London Breast Institute, The Princess Grace Hospital, London, UK

    K. Mokbel

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  1. W. Sasi
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  2. L. Ye
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  3. W. G. Jiang
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  4. K. Mokbel
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  5. A. Sharma
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Correspondence to W. Sasi.

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Sasi, W., Ye, L., Jiang, W.G. et al. Observations on the effects of Suppressor of Cytokine Signaling 7 (SOCS7) knockdown in breast cancer cells: their in vitro response to Insulin Like Growth Factor I (IGF-I). Clin Transl Oncol 16, 476–487 (2014). https://doi.org/10.1007/s12094-013-1107-0

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  • DOI: https://doi.org/10.1007/s12094-013-1107-0

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