Ethanol enhances the interaction of breast cancer cells over-expressing ErbB2 with fibronectin.

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.

• Authors: Mei Xu, Kimberly A Bower, Gang Chen, Xianglin Shi, Zheng Dong, Zunji Ke, Jia Luo
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 34 Issue 5 Pg. 751-60 (May 2010) ISSN: 1530-0277 [Electronic] England
• PMID: 20201928 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Fibronectins
• Ethanol
• Receptor, ErbB-2
• Focal Adhesion Kinase 1
• PTK2 protein, human

Topics

• Breast Neoplasms (enzymology, metabolism, pathology)
• Cell Adhesion (drug effects, physiology)
• Cell Line, Tumor
• Ethanol (pharmacology)
• Female
• Fibronectins (metabolism)
• Focal Adhesion Kinase 1 (physiology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Protein Binding (drug effects, physiology)
• Receptor, ErbB-2 (biosynthesis, metabolism, physiology)