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NF-kappaB and estrogen receptor alpha interactions: Differential function in estrogen receptor-negative and -positive hormone-independent breast cancer cells.
J Cell Biochem. 2009 Jun 01; 107(3):448-59.JC

Abstract

Estrogen receptor (ER)-positive breast cancer cells have low levels of constitutive NF-kappaB activity while ER negative (-) cells and hormone-independent cells have relatively high constitutive levels of NF-kappaB activity. In this study, we have examined the aspects of mutual repression between the ERalpha and NF-kappaB proteins in ER+ and ER- hormone-independent cells. Ectopic expression of the ERalpha reduced cell numbers in ER+ and ER- breast cancer cell lines while NF-kappaB-binding activity and the expression of several NF-kappaB-regulated proteins were reduced in ER- cells. ER overexpression in ER+/E2-independent LCC1 cells only weakly inhibited the predominant p50 NF-kappaB. GST-ERalpha fusion protein pull downs and in vivo co-immunoprecipitations of NF-kappaB:ERalpha complexes showed that the ERalpha interacts with p50 and p65 in vitro and in vivo. Inhibition of NF-kappaB increased the expression of diverse E2-regulated proteins. p50 differentially associated directly with the ER:ERE complex in LCC1 and MCF-7 cells by supershift analysis while p65 antibody reduced ERalpha:ERE complexes in the absence of a supershift. ChIP analysis demonstrated that NF-kappaB proteins are present on an endogenous ERE. Together these results demonstrate that the ER and NF-kappaB undergo mutual repression, which may explain, in part, why expression of the ERalpha in ER- cells does not confer growth signaling. Secondly, the acquisition of E2-independence in ER+ cells is associated with predominantly p50:p50 NF-kappaB, which may reflect alterations in the ER in these cells. Since the p50 homodimer is less sensitive to the presence of the ER, this may allow for the activation of both pathways in the same cell.

Authors+Show Affiliations

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19350539

Citation

Gionet, Nathalie, et al. "NF-kappaB and Estrogen Receptor Alpha Interactions: Differential Function in Estrogen Receptor-negative and -positive Hormone-independent Breast Cancer Cells." Journal of Cellular Biochemistry, vol. 107, no. 3, 2009, pp. 448-59.
Gionet N, Jansson D, Mader S, et al. NF-kappaB and estrogen receptor alpha interactions: Differential function in estrogen receptor-negative and -positive hormone-independent breast cancer cells. J Cell Biochem. 2009;107(3):448-59.
Gionet, N., Jansson, D., Mader, S., & Pratt, M. A. (2009). NF-kappaB and estrogen receptor alpha interactions: Differential function in estrogen receptor-negative and -positive hormone-independent breast cancer cells. Journal of Cellular Biochemistry, 107(3), 448-59. https://doi.org/10.1002/jcb.22141
Gionet N, et al. NF-kappaB and Estrogen Receptor Alpha Interactions: Differential Function in Estrogen Receptor-negative and -positive Hormone-independent Breast Cancer Cells. J Cell Biochem. 2009 Jun 1;107(3):448-59. PubMed PMID: 19350539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF-kappaB and estrogen receptor alpha interactions: Differential function in estrogen receptor-negative and -positive hormone-independent breast cancer cells. AU - Gionet,Nathalie, AU - Jansson,Deidre, AU - Mader,Sylvie, AU - Pratt,M A Christine, PY - 2009/4/8/entrez PY - 2009/4/8/pubmed PY - 2009/9/2/medline SP - 448 EP - 59 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 107 IS - 3 N2 - Estrogen receptor (ER)-positive breast cancer cells have low levels of constitutive NF-kappaB activity while ER negative (-) cells and hormone-independent cells have relatively high constitutive levels of NF-kappaB activity. In this study, we have examined the aspects of mutual repression between the ERalpha and NF-kappaB proteins in ER+ and ER- hormone-independent cells. Ectopic expression of the ERalpha reduced cell numbers in ER+ and ER- breast cancer cell lines while NF-kappaB-binding activity and the expression of several NF-kappaB-regulated proteins were reduced in ER- cells. ER overexpression in ER+/E2-independent LCC1 cells only weakly inhibited the predominant p50 NF-kappaB. GST-ERalpha fusion protein pull downs and in vivo co-immunoprecipitations of NF-kappaB:ERalpha complexes showed that the ERalpha interacts with p50 and p65 in vitro and in vivo. Inhibition of NF-kappaB increased the expression of diverse E2-regulated proteins. p50 differentially associated directly with the ER:ERE complex in LCC1 and MCF-7 cells by supershift analysis while p65 antibody reduced ERalpha:ERE complexes in the absence of a supershift. ChIP analysis demonstrated that NF-kappaB proteins are present on an endogenous ERE. Together these results demonstrate that the ER and NF-kappaB undergo mutual repression, which may explain, in part, why expression of the ERalpha in ER- cells does not confer growth signaling. Secondly, the acquisition of E2-independence in ER+ cells is associated with predominantly p50:p50 NF-kappaB, which may reflect alterations in the ER in these cells. Since the p50 homodimer is less sensitive to the presence of the ER, this may allow for the activation of both pathways in the same cell. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/19350539/NF_kappaB_and_estrogen_receptor_alpha_interactions:_Differential_function_in_estrogen_receptor_negative_and__positive_hormone_independent_breast_cancer_cells_ L2 - https://doi.org/10.1002/jcb.22141 DB - PRIME DP - Unbound Medicine ER -