Role of matrix metalloproteinase-2 in ethanol-induced invasion by breast cancer cells

Jia Luo

doi:10.1111/j.1440-1746.2006.04578.x

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Role of matrix metalloproteinase-2 in ethanol-induced invasion by breast cancer cells

Journal article

Peer reviewed

Role of matrix metalloproteinase-2 in ethanol-induced invasion by breast cancer cells

Jia Luo

Journal of gastroenterology and hepatology, Vol.21 Suppl 3(s3), pp.S65-S68

10/2006

DOI: 10.1111/j.1440-1746.2006.04578.x

PMID: 16958676

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Abstract

Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying cellular/molecular mechanisms remain unknown. Amplification of ErbB2, a receptor tyrosine kinase, is found in 20-30% of breast cancer patients. Ethanol preferably stimulates invasion by breast cancer cells over-expressing ErbB2 in vitro. Over-expression of ErbB2 is positively associated with elevated levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Ethanol at physiologically relevant concentrations activates MMP-2 without altering its expression level in mammary epithelial cells over-expressing ErbB2, but not in cells expressing low levels of ErbB2. The activation is dependent on c-jun N-terminal kinases (JNK) and reactive oxygen species. Selective inhibitors of MMP-2 and anti-oxidants significantly inhibit ethanol-stimulated cell invasion. Similarly, knocking down MMP-2 by small interference RNA induces a partial blockage on ethanol-promoted cell invasion. Matrix metalloproteinase-2 is predominantly expressed in stromal fibroblasts; ethanol also activates fibroblastic MMP-2. The conditioned medium collected from ethanol-exposed fibroblasts dramatically stimulates the invasion of breast cancer cells. The role of MMP-2 in ethanol-induced tumor promotion is discussed.

Epithelial Cells - enzymology

Ethanol - pharmacology

Gene Expression Regulation

Genes, erbB-2

Humans

JNK Mitogen-Activated Protein Kinases - metabolism

Mammary Glands, Human - cytology

Mammary Glands, Human - enzymology

Matrix Metalloproteinase 2 - metabolism

Matrix Metalloproteinase 9 - metabolism

p38 Mitogen-Activated Protein Kinases - metabolism

Phosphatidylinositol 3-Kinases - metabolism

Reactive Oxygen Species - metabolism

Receptor, ErbB-2 - genetics

Transcription, Genetic

Up-Regulation

Details

Title: Subtitle: Role of matrix metalloproteinase-2 in ethanol-induced invasion by breast cancer cells
Creators: Jia Luo - West Virginia University
Resource Type: Journal article
Publication Details: Journal of gastroenterology and hepatology, Vol.21 Suppl 3(s3), pp.S65-S68
DOI: 10.1111/j.1440-1746.2006.04578.x
PMID: 16958676
ISSN: 0815-9319
eISSN: 1440-1746
Grant note: AA015407 / NIAAA NIH HHS AA013984 / NIAAA NIH HHS CA90385 / NCI NIH HHS
Language: English
Date published: 10/2006
Academic Unit: Pathology
Record Identifier: 9984186563502771

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