MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2

Zunji Ke; Hong Lin; Zhiqin Fan; Tian-Quan Cai; Rebecca A Kaplan; Cuiling Ma; Kimberly A Bower; Xianglin Shi; Jia Luo

doi:10.1002/ijc.21769

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MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2

Journal article

Peer reviewed

MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2

Zunji Ke, Hong Lin, Zhiqin Fan, Tian-Quan Cai, Rebecca A Kaplan, Cuiling Ma, Kimberly A Bower, Xianglin Shi and Jia Luo

International journal of cancer, Vol.119(1), pp.8-16

07/01/2006

DOI: 10.1002/ijc.21769

PMID: 16450376

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Abstract

Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. We have previously demonstrated that over-expression of ErbB2 promoted ethanol-mediated invasion of mammary epithelial cells and breast cancer cells. However, the underlying cellular/molecular mechanisms remain unknown. By gelatin zymography, we showed that over-expression of ErbB2 increased the production of matrix metalloproteinase-2 (MMP-2) and MMP-9 in human mammary epithelial cells (HB2). Transient or stable transfection of ErbB2 cDNA to HB2 cells upregulated the transcripts and the activity of the MMP-2/-9 gene promoter; the upregulation of MMP-2/-9 expression was mediated by p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (PI3K). Although ethanol, at physiologically relevant concentrations (100-400 mg/dl), did not affect the production of MMP-2/-9, it activated MMP-2 in HB2 cells over-expressing ErbB2 (HB2(ErbB2)), but not HB2 cells; it enhanced the cleavage of proform MMP-2 (72 kDa) to an active form (62 kDa). The activation was dependent on c-jun N-terminal kinases (JNKs) and reactive oxygen species (ROS). On the other hand, ethanol affected neither the expression nor the activation of MMP-9. Selective inhibitors of MMP-2 (SB-3CT and OA-Hy) and antioxidants significantly inhibited ethanol-stimulated invasion of HB2(ErbB2) cells. Furthermore, knocking down MMP-2 by small interference RNA also induced a partial blockage on ethanol-promoted invasion of HB2(ErbB2) cells. Thus, ethanol-stimulated invasion of cells over-expressing ErbB2 was mediated, at least partially, by MMP-2 activation.

Blotting, Western

Cell Culture Techniques

Epithelial Cells - enzymology

Ethanol - pharmacology

Female

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

Polymerase Chain Reaction

Reactive Oxygen Species - metabolism

Receptor, ErbB-2 - genetics

Transcription, Genetic

Up-Regulation

Details

Title: Subtitle: MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2
Creators: Zunji Ke - Chinese Academy of Sciences
Hong Lin - West Virginia University
Zhiqin Fan - Chinese Academy of Sciences
Tian-Quan Cai
Rebecca A Kaplan - Merck & Co.
Cuiling Ma - West Virginia University
Kimberly A Bower - West Virginia University
Xianglin Shi - Chinese Academy of Sciences
Jia Luo - West Virginia University
Resource Type: Journal article
Publication Details: International journal of cancer, Vol.119(1), pp.8-16
DOI: 10.1002/ijc.21769
PMID: 16450376
NLM abbreviation: Int J Cancer
ISSN: 0020-7136
eISSN: 1097-0215
Grant note: AA12968 / NIAAA NIH HHS CA96385 / NCI NIH HHS
Language: English
Date published: 07/01/2006
Academic Unit: Pathology
Record Identifier: 9984186629802771

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