Introduction: Alcohol consumption increases breast cancer risk in women. Additionally, alcohol increases the metastatic ability of cancer cells. Metastasis suppressor genes encode proteins that have the ability to slow down or prevent the invasiveness of cancer cells, thus inhibiting the establishment of metastases. We analyzed the expression level of metastasis suppressor genes to determine the mechanisms by which alcohol increases the invasive ability of breast cancer cells.

Methods: The invasiveness, or metastatic ability, of breast cancer cells was determined by the Boyden assay. To determine if alcohol increases invasion of breast cancer cells via the metastasis suppressor gene Nm23, we over-expressed or down-regulated Nm23 using siRNA-mediated knockdown; subsequently, we determined the effects of alcohol on the invasiveness of these cancer cells.

Results: Results show that alcohol increased breast cancer cell invasion in a dose-dependent manner. Alcohol significantly decreased the expression of Nm23. Overexpression of Nm23 in breast cancer cells suppressed the effects of alcohol on the invasive ability of the cancer cells. Also, exposure of cancer cells to alcohol led to an increase in the expression level of the fibronectin receptor subunit ITGA5, and overexpression of Nm23 blocked the effects of alcohol. Further, the invasiveness of the breast cancer cells was inhibited when ITGA5 was knocked down by siRNA, and alcohol was unable to increase the invasiveness of the cancer cells when ITGA5 was knocked down.

Conclusions: Results suggest that alcohol increases the invasive ability of breast cancer cells by down-regulating the metastatic suppressor Nm23 gene, which leads to increased expression of ITGA5. Consequently, up-regulated ITGA5 may increase the invasive ability of the cancer cells.

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A100.