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

Abstract

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.

MCF-7 Breast Cancer Cell Line, a Model for the Study of the Association Between Inflammation and ABCG2-Mediated Multi Drug Resistance

“…This shows that IL-6 probably modulates ABCG2 expression by affecting ABCG2 protein translation and/or stability, but not ABCG2 transcription. For unknown reasons, this modulation did not result in the increased activity of the protein (Mosaffa et al, 2009). In contrast to the results obtained for MCF-7 cells, in its mitoxantrone-resistance derivative, MCF-7/MX cells, none of the cytokines (even at high concentrations and long incubation times) exerted significant effects on ABCG2 mRNA levels.…”

“…In contrast to the results obtained for MCF-7 cells, in its mitoxantrone-resistance derivative, MCF-7/MX cells, none of the cytokines (even at high concentrations and long incubation times) exerted significant effects on ABCG2 mRNA levels. Because MCF-7/MX cells overexpress ABCG2 mRNA, it is likely that although modulation of the signaling pathway(s) responsible for increased transcription of ABCG2 in IL-1 and TNF--treated MCF-7 cells, has already happened in MCF-7/MX cells, but treatment with these cytokines could not cause further induction in ABCG2 mRNA levels (Mosaffa et al, 2009). The results showed that IL-1 increased ABCG2 function and TNF-enhanced both ABCG2 protein expression and function in MCF-7/MX cells.…”

“…The results showed that IL-1 increased ABCG2 function and TNF-enhanced both ABCG2 protein expression and function in MCF-7/MX cells. This lack of correspondence between mRNA and expression/function data suggests that perhaps in addition to the transcriptional regulatory effects of IL-1 and TNF-, these two cytokines can also mediate ABCG2 expression and function via translational and/or post-translational effects (Mosaffa et al, 2009). …”

Phorbol Ester TPA Modulates Chemoresistance in the Drug Sensitive Breast Cancer Cell Line MCF-7 by Inducing Expression of Drug Efflux Transporter ABCG2

“…Energy dependent drug efflux involving ABCG2 is believed to result in reduced drug accumulation and sensitivity to a variety of natural products used in the treatment of cancers. We have previously showed that proinflammatory cytokines IL-1β and TNF-α induced ABCG2 and pregnane X receptor (PXR) expression in breast cancer cell line MCF-7 (Mosaffa et al, 2009;Malekshah et al, 2011). In another study, it has been indicated that dexamethasone (an anti-inflammatory drug) reduced the Asian Pacific Journal of Cancer Prevention, Vol 13, 2012 2983 DOI:http://dx.doi.org/10.7314/APJCP.2012.13.6.2979 Cells through the ABCG2 Drug Efflux Transporter expression of ABCG2 mRNA in MCF-7 and MCF-7/ MX breast cancer cell lines.…”

“…In the drug resistant MCF7/MX cells, ABCG2 is already overexpressed, and its expression may be at a threshold maximum level. Perhaps an induction with TPA treatment may not be causing any detectable increase in mRNA level (Elahian et al, 2009;Mosaffa et al, 2009).…”