Abstract
The present study aims to determine the role of γ-aminobutyric acid (GABA) signaling molecules in breast cancer metastasis. Our results reveal that GABAergic system exists in breast cancer cells. Both the GABA synthetic enzyme. (GAD65/67) and GABAB receptor are expressed in 4T1 mouse breast cancer cells, MCF-7 human breast cancer cells and human breast cancer tissue. Baclofen, a GABABR agonist, significantly promoted 4T1 cells invasion and migration in vitro and metastasis in vivo, an event that was attenuated by GABABR antagonist CGP55845. Baclofen-induced breast cancer metastasis was mediated by ERK1/2 pathway.
Keywords:
Breast cancer; ERK; GABA receptor; Metastasis; γ-Aminobutyric acid.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Breast Neoplasms / enzymology*
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Breast Neoplasms / pathology*
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Cell Movement* / drug effects
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Dose-Response Relationship, Drug
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Female
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GABA-B Receptor Agonists / pharmacology
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GABA-B Receptor Antagonists / pharmacology
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Glutamate Decarboxylase / metabolism
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Humans
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Lung Neoplasms / enzymology*
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Lung Neoplasms / secondary*
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MCF-7 Cells
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Matrix Metalloproteinase 2 / metabolism
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Neoplasm Invasiveness
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Phosphorylation
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Receptors, GABA-B / drug effects
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Receptors, GABA-B / metabolism
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Signal Transduction* / drug effects
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Time Factors
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gamma-Aminobutyric Acid / metabolism*
Substances
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GABA-B Receptor Agonists
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GABA-B Receptor Antagonists
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Receptors, GABA-B
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gamma-Aminobutyric Acid
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MAPK1 protein, human
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Mapk1 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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MMP2 protein, human
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Matrix Metalloproteinase 2
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Mmp2 protein, rat
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Glutamate Decarboxylase
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glutamate decarboxylase 1
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glutamate decarboxylase 2