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Abstract Background: Patients with estrogen receptor (ER) -positive breast cancers are generally treated with endocrine therapy, but in a considerable fraction of patients resistance occurs. Previous research showed that nuclear factor kappa B (NFkB) may play a role in the development of resistance to hormonal therapy. In this study, we investigated the role of NFkB, and its interaction with ER in the development of endocrine resistance by studying breast cancer cell lines with variable ER and NFkB activity. Material and methods: Three gene expression data sets of breast cancer cell lines (GSE12777: Hoeflich et al, 2009; GSE16795: Hollestelle et al, 2009; E-TAM-157: Neve et al, 2005) were retrieved from Gene Expression Omnibus or ArrayExpress. The expression profiles were screened for ER and NFkB target genes to identify cell lines with strong and weak activation of ER and NFkB. Based on these activation profiles, 8 cell lines (MCF7, BT20, CAMA1, MDA-MB-361, MDA-MB-231, MDA-MB-134, MDA-MB-468 and MDA-MB-436) with high and low ER and NFkB activation profiles were selected. Using qRT-PCR on RNA from these cell lines, the expression of 6 biomarkers for endocrine resistance (ADAMDEC1, ITK, ABAT, CLEC7A, ETS1 and STC2) were profiled. 18S and beta-Actin were used as housekeeping genes. Relative expression levels were analyzed in function of ER and NFkB activation. Results: There is a significant lower expression of ADAMDEC1 (P=0. 011), ITK (P=0. 012) and ETS1 (P0. 001) in the ER-positive cell lines compared to the ER-negative ones, while ABAT (P0. 001) and STC2 (P=0. 049) are significant higher expressed in ER-positive cell lines. Comparison of ER-positive/NFkB-negative with ER-positive/NFkB-positive cell lines revealed a difference in expression in 3 of the 6 genes, namely ADAMDEC1 (P=0. 037), ITK (P=0. 013) and ABAT (P=0. 014), showing a higher expression in the double positive cell lines. Conclusion: The construction of a set of breast cancer cell lines with different patterns of combined ER-NFkB activity is a useful tool to unravel the mechanism of ER and NFkB interaction leading to endocrine resistance. In this context, the number of cell lines will be expended. With respect to our data, the expression profiles of ADAMDEC1 and ITK were in line with the expected attenuated responsiveness of the NFkB-positive breast cancer cells to endocrine therapy and therefore might play a role in NFkB-driven resistance to endocrine therapy. Citation Format: Authors. Abstract title abstract. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72 (8 Suppl): Abstract nr 3919. doi: 1538-7445. AM2012-3919
Sas et al. (Sun,) studied this question.