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Author Notes:

Shaojin You: Email: shoajin.you@va.gov Qiong Chen: Email: qiongch@163.com

The authors thank Dr. Peter Thomas (Marine Science Institute, University of Texas at Austin) for providing mPRα plasmid and kind consultancy and Dr. Hima Bindu Chunduri and Dr. Prem Sharma (Atlanta Research & Educational Foundation, Atlanta VA Medical Center, GA) for their assistance in plasmid DNA isolation. This study was supported by the Emory University Research ACTSI Award (S. You), Atlanta Research and Education Foundation Bridge Fund (S. You), and China Scholarship Council and Central South University (Mingxuan Xie and Qiong Chen).

The authors declare that they have no competing interests.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biotechnology & Applied Microbiology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • RANDOMIZED CONTROLLED-TRIAL
  • CENTRAL-NERVOUS-SYSTEM
  • FOCAL ADHESION KINASE
  • ALPHA MPR-ALPHA
  • MEDROXYPROGESTERONE ACETATE
  • POSTMENOPAUSAL WOMEN
  • MEGESTROL-ACETATE
  • BRAIN METASTASES
  • STEROID-HORMONES
  • GENE-EXPRESSION

Progesterone and Src Family Inhibitor PP1 Synergistically Inhibit Cell Migration and Invasion of Human Basal Phenotype Breast Cancer Cells

Tools:

Journal Title:

BioMed Research International

Volume:

Volume 2015

Publisher:

, Pages 426429-426429

Type of Work:

Article | Final Publisher PDF

Abstract:

Basal phenotype breast cancer is one of the most aggressive breast cancers that frequently metastasize to brain. The role of sex hormones and their receptors in development of this disease is largely unclear. We demonstrated that mPR was expressed at a moderate level in a brain metastatic BPBC cell line MB231Br, which was derived from the parent mPR undetectable MB231 cells. It functioned as an essential mediator for progesterone induced inhibitory effects on cell migration of MB231Br and, when coincubated with PP1, synergistically enhanced the progesterone's inhibitory effect on cell migration and invasion in vitro. Progesterone and PP1 cotreatment induced a cascade of molecular signaling events, such as dephosphorylation of FAK, downregulation of MMP9, VEGF, and KCNMA1 expressions. Our in vitro study demonstrated that mPR was expressed and functioned as an essential mediator for progesterone induced inhibitory effects on cell migration and invasion in BPBC cells. This inhibitory effect was enhanced by PP1 via FAK dephosphorylation, MMP9, VEGF, and KCNMA1 downregulation mechanisms. Our study provides a new clue toward the development of novel promising agents and pathways for inhibiting nuclear hormonal receptor-negative and endocrine-resistant breast cancers.

Copyright information:

© 2015 Mingxuan Xie et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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