Interleukin-1 beta and tumor necrosis factor-alpha increase ABCG2 expression in MCF-7 breast carcinoma cell line and its mitoxantrone-resistant derivative, MCF-7/MX.

OBJECTIVE

In this study, we aimed to evaluate the influence of proinflammatory cytokines on ABCG2 expression and function in human MCF-7 breast cancer cell line and its mitoxantrone-resistant derivative MCF-7/MX.

METHODS

The effects of proinflammatory cytokines on ABCG2 mRNA expression were studied using real-time PCR method. Cytokine-mediated modification of ABCG2 protein expression and function was investigated by means of flow cytometry.

RESULTS

Significant inductions in the ABCG2 mRNA levels, protein expression, and activity were observed in IL-1 beta and TNF-alpha-treated MCF-7 cells. IL-6 increased ABCG2 protein, but had no effects on ABCG2 mRNA and function in MCF-7 cells. Although IL-1 beta did not alter mRNA and protein levels of the transporter in MCF-7/MX cells, ABCG2-mediated efflux was significantly increased in IL-1 beta-treated MCF-7/MX cells. TNF-alpha-treated MCF-7/MX cells also demonstrated greater ABCG2 protein expression and function without any changes in mRNA levels of the transporter. Neither ABCG2 mRNA nor its protein expression and function were affected by IL-6 in MCF-7/MX cells.

CONCLUSION

IL-1 beta and TNF-alpha induce ABCG2 mRNA and protein expression and increase its activity in breast cancer cell line MCF-7. In MCF-7/MX cells these cytokines modulate ABCG2 protein expression and/or function, but they have no influence on the transporter mRNA levels.