Repression of breast cancer cell growth by proteasome inhibitors in vitro: impact of mitogen-activated protein kinase phosphatase 1

Cancer Biology & Therapy
Brijeshkumar S PatelAlaina J Ammit

Abstract

Mitogen activated protein kinase phosphatase-1 (MKP-1) has emerged as an important protein mediating breast cancer oncogenesis and chemoresistance to cancer chemotherapies, especially proteasome inhibitors. In this in vitro study, we utilized the breast cancer epithelial cell lines MCF-7 and MDA-MB-231, in comparison to MCF-10A control cells, to examine the impact of MKP-1 on breast cancer cell growth and repression by proteasome inhibitors. We confirm that proteasome inhibitors MG-132 and bortezomib induce MKP-1 protein upregulation and we show that one of the ways in which bortezomib increases MKP-1 in breast cancer cells, in addition to inhibition of ubiquitin-proteasome system, is via upregulation of MKP-1 mRNA expression in p38 MAPK-mediated manner. Notably, these effects are specific to cancer cells, as bortezomib activated p38 MAPK and induced MKP-1 in MCF-7 and MDA-MB-231 breast cancer cells, but not in control cells (MCF-10A). We took a dual approach toward targeting MKP-1 to show that bortezomib-induced effects are enhanced. Firstly, treatment with the non-specific MKP-1 inhibitor triptolide reduces breast cancer cell growth and augments proteasome inhibitor-induced effects. Secondly, specific knock-down of MKP-1 with...Continue Reading

References

Jan 1, 1991·Molecular Carcinogenesis·F BasoloA J Klein-Szanto
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peili ChenYusen Liu
Jun 17, 2005·The New England Journal of Medicine·Paul G RichardsonUNKNOWN Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators
Jan 13, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C H YangM Cristofanilli
Sep 19, 2006·Cellular Signalling·Jun-Hao HuBao-Xue Ge
Sep 27, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Richard I FisherAndré Goy
Jul 22, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S CrestaL Gianni
Sep 27, 2008·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·David J McConkey, Keyi Zhu
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Federico RojoJoan Albanell
Jun 16, 2009·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Jing LiuLuyong Zhang
Jan 30, 2010·Cancer Metastasis Reviews·Kelly K Haagenson, Gen Sheng Wu
Jan 25, 2011·International Immunopharmacology·Qiuyan Liu
Jun 26, 2012·Progress in Molecular Biology and Translational Science·Boris Cvek

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Citations

Sep 13, 2015·Molecular and Cellular Endocrinology·Jerry Vriend, Russel J Reiter
Aug 13, 2017·The Biochemical Journal·Matthias DedobbeleerBernard Rogister
May 1, 2021·Cells·Margarita L Martinez-Fierro, Idalia Garza-Veloz

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Methods Mentioned

BETA
transfection
ubiquitination

Related Concepts