PXR and NF-κB correlate with the inducing effects of IL-1β and TNF-α on ABCG2 expression in breast cancer cell lines

Eur J Pharm Sci. 2012 Sep 29;47(2):474-80. doi: 10.1016/j.ejps.2012.06.011. Epub 2012 Jun 29.

Abstract

In this study we aimed to evaluate PXR and ABCG2 gene expression patterns and NF-κB activity induced by proinflammatory cytokines in different breast normal and carcinoma cells. The effects of proinflammatory cytokines on ABCG2 and PXR mRNA expression were studied using real-time PCR. Western blot analysis used for evaluating the protein levels of ABCG2, PXR and the active form of NF-κB (p65 in nuclear protein extract). Significant inductions in the ABCG2 and PXR mRNA and protein levels and NF-κB activity, were observed in MCF7, BT-474, CAL51, 184A1 and HBL100 cells, upon treatment with 50 ng/ml of IL-1β and TNF-α. On the contrary significant reduction of the ABCG2 and PXR mRNA and protein levels and NF-κB activity, were observed in MDA-MB-435 cell line. In conclusion, IL-1β and TNF-α induced ABCG2 and PXR expression and NF-κB activity in some breast cancer and normal cell lines. Similar patterns of induction and reduction in PXR and ABCG2 genes and NF-κB activity suggest a probable relationship between ABCG2, PXR and NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Female
  • Humans
  • Interleukin-1beta / pharmacology*
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Pregnane X Receptor
  • RNA, Messenger / metabolism
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Interleukin-1beta
  • NF-kappa B
  • Neoplasm Proteins
  • Pregnane X Receptor
  • RNA, Messenger
  • Receptors, Steroid
  • Tumor Necrosis Factor-alpha