Journal article
Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 With Fibronectin
Alcoholism, clinical and experimental research, Vol.34(5), pp.751-760
Received for publication August 18, 2009; accepted December 3, 2009.
05/2010
DOI: 10.1111/j.1530-0277.2010.01147.x
PMCID: PMC4981247
PMID: 20201928
Abstract
Background: Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying cellular/molecular mechanisms remain unknown. Amplification of ErbB2 or HER2, a receptor tyrosine kinase of the ErbB family, is found in 20 to 30% of patients with breast cancer. We have previously demonstrated that the effect of ethanol on the migration/invasion of breast cancer cells positively correlated with the expression levels of ErbB2. Adhesion to the extracellular matrix (ECM) is an important initial step for cancer cell invasion and metastasis. In this study, we investigated the effects of ethanol on the adhesion of MCF7 breast cancer cells over-expressing ErbB2 (MCF7(ErbB2)) to human plasma fibronectin.
Methods: To test the hypothesis that ethanol may enhance the attachment of human breast cancer cells to fibronectin, an important component of the ECM, we evaluated the effect of ethanol on the expression of focal adhesions, cell attachment, and ErbB2 signaling in cultured MCF7(ErbB2) cells.
Results: Exposure to ethanol drastically enhanced the adhesion of MCF(ErbB2) cells to fibronectin and increased the expression of focal adhesions. Ethanol induced phosphorylation of ErbB2 at Tyr1248, FAK at Tyr861, and cSrc at Try216. Ethanol promoted the interaction among ErbB2, FAK, and cSrc, and the formation of a focal complex. AG825, a selective ErbB2 inhibitor, attenuated the ethanol-induced phosphorylation of ErbB2 and its association with FAK. Furthermore, AG825 blocked ethanol-promoted cell/fibronectin adhesion as well as the expression of focal adhesions.
Conclusions: Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex.
Details
- Title: Subtitle
- Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 With Fibronectin
- Creators
- Mei Xu - University of KentuckyKimberly A Bower - University of KentuckyGang Chen - University of KentuckyXianglin Shi - University of KentuckyZheng Dong - University of KentuckyZunji Ke - Institute for Biological SciencesJia Luo - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.34(5), pp.751-760
- Edition
- Received for publication August 18, 2009; accepted December 3, 2009.
- DOI
- 10.1111/j.1530-0277.2010.01147.x
- PMID
- 20201928
- PMCID
- PMC4981247
- NLM abbreviation
- Alcohol Clin Exp Res
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Publisher
- Blackwell Publishing Ltd
- Number of pages
- 10
- Language
- English
- Date published
- 05/2010
- Academic Unit
- Pathology
- Record Identifier
- 9984186549502771
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