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

• Type of Material: Article
• Authors: Mingxuan Xie, Central South University; Li Zhou, Shanghai Seventh Peoples Hosp; Xi Chen, Central South University; Lindsey O. Gainey, Atlanta Research & Educational Foundation; Jian Xiao, Central South University; Mark Nanes, Emory University; Anji Hou, Shanghai Seventh Peoples Hosp; Shaojin You, Atlanta Research & Educational Foundation; Qiong Chen, Central South University
• Language: English
• Date: 2015-05-17
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Mingxuan Xie et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1155/2015/426429
• Title of Journal or Parent Work: BioMed Research International
• ISSN: 2314-6133
• Volume: 2015
• Start Page: 426429
• End Page: 426429
• Keywords: MEDROXYPROGESTERONE ACETATE; RANDOMIZED CONTROLLED-TRIAL; Life Sciences & Biomedicine; STEROID-HORMONES; BRAIN METASTASES; GENE-EXPRESSION; Medicine, Research & Experimental; CENTRAL-NERVOUS-SYSTEM; FOCAL ADHESION KINASE; ALPHA MPR-ALPHA; Biotechnology & Applied Microbiology; POSTMENOPAUSAL WOMEN; Research & Experimental Medicine; MEGESTROL-ACETATE; Science & Technology
• Research Categories: Biology, Cell; Biology, Molecular; Health Sciences, Oncology

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.