The estrogen receptor functions as an inhibitor of NF-kappaB

Title: The estrogen receptor functions as an inhibitor of NF-kappaB
Authors: Gionet, Nathalie
Date: 2007
Abstract: The development of antiestrogen resistance has been correlated with changes in ERalpha expression/mutation and a rise in NF-kappaB activity. We believe that NF-kappaB is activated in both ER-positive and ER-negative breast cancer cells and that it is attenuated by liganded ERalpha in ER-positive cells by regulating the formation of p50 and p65 complexes. It is possible that mutations in the ER alter its ability to bind and regulate NF-kappaB activity, which allows constitutive activation of NF-kappaB and confers estrogen-independence to these cells. Here, we demonstrate that increased expression of ER in both ER-negative as well as ER-positive cells results in decreased cell viability and decreased NF-kappaB activity. We also confirm a direct interaction between ERalpha and NF-kappaB subunits in vitro. We also demonstrate that NF-kappaB subunits, p65 and p50, are capable of interacting with ERalpha on an ERE in vivo and that this interaction is enhanced by treatment with E2. Moreover we are the first to show that inhibition of NF-kappaB results in increased ER activity, indicating a possible mutual repression between ERalpha and NF-kappaB. Lastly, we demonstrate that treatment with tamoxifen does not have the same inhibitory effects on NF-kappaB as does estrogen. Together, these observations suggest that an interaction between ERalpha and NF-kappaB have a vital role in the development of breast cancer, estrogen-independent growth and resistance to antiestrogens.
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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