Format

Send to

Choose Destination
Cancer Res. 2009 Dec 1;69(23):8918-25. doi: 10.1158/0008-5472.CAN-09-2608. Epub 2009 Nov 17.

Positive cross-talk between estrogen receptor and NF-kappaB in breast cancer.

Author information

1
Department of Physiology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. jfrasor@uic.edu

Erratum in

  • Cancer Res. 2010 Jan 15;70(2):854.
  • Cancer Res. 2010 Mar 1;70(5):2140.

Abstract

Estrogen receptors (ER) and nuclear factor-kappaB (NF-kappaB) are known to play important roles in breast cancer, but these factors are generally thought to repress each other's activity. However, we have recently found that ER and NF-kappaB can also act together in a positive manner to synergistically increase gene transcription. To examine the extent of cross-talk between ER and NF-kappaB, a microarray study was conducted in which MCF-7 breast cancer cells were treated with 17beta-estradiol (E(2)), tumor necrosis factor alpha (TNFalpha), or both. Follow-up studies with an ER antagonist and NF-kappaB inhibitors show that cross-talk between E(2) and TNFalpha is mediated by these two factors. We find that although transrepression between ER and NF-kappaB does occur, positive cross-talk is more prominent with three gene-specific patterns of regulation: (a) TNFalpha enhances E(2) action on approximately 30% of E(2)-upregulated genes; (b) E(2) enhances TNFalpha activity on approximately 15% of TNFalpha-upregulated genes; and (c) E(2) + TNFalpha causes a more than additive upregulation of approximately 60 genes. Consistent with their prosurvival roles, ER and NF-kappaB and their target gene, BIRC3, are involved in protecting breast cancer cells against apoptosis. Furthermore, genes positively regulated by E(2) + TNFalpha are clinically relevant because they are enriched in luminal B breast tumors and their expression profiles can distinguish a cohort of patients with poor outcome following endocrine treatment. Taken together, our findings suggest that positive cross-talk between ER and NF-kappaB is more extensive than anticipated and that these factors may act together to promote survival of breast cancer cells and progression to a more aggressive phenotype.

PMID:
19920189
PMCID:
PMC2996265
DOI:
10.1158/0008-5472.CAN-09-2608
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center