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Effects of Estrogen and Tamoxifen on Ishikawa cells after 24h and 48h

ABSTRACT: Treatment with the breast cancer drug tamoxifen confers a risk of developing uterine tumors or other endometrial pathologies. Tamoxifen is a selective estrogen receptor modulator, which demonstrates tissue-specific activity although the mechanisms remain poorly understood. Both estradiol and tamoxifen act as estrogen agonists on the human uterus, and therefore have the potential to promote carcinogenicity. Estradiol and tamoxifen elicit cellular responses via the estrogen receptors (ER), which are involved in multiple signalling pathways. The effects at the molecular level are further influenced by the differential recruitment of co-factors and the presence of specific promoter motifs in target genes. In this study, ER positive (+) Ishikawa cells are used as a model to investigate the overall effect of treatment with either 17b-estradiol or 4-hydroxytamoxifen on the gene expression profiles. Keywords: Comparison of estradiol and tamoxifen on Ishikawa human uterine cells after 24h or 48h

ORGANISM(S): Homo sapiens

PROVIDER: GSE3762 | GEO | 2006/02/01

SECONDARY ACCESSION(S): PRJNA93937

REPOSITORIES: GEO

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Project description:Estrogen receptors play critical roles in both the normal physiological, and disease states of numerous tissues, including breast and uterus. Estrogen receptor alpha (ER) can activate or repress the expression of target genes upon estrogen stimulation. In order to better understand the transcriptional network of ER in breast and uterus, we generated genome wide maps ofM-BM- ER binding sites (ERBS) and gene expression profiles in breast cancer cells (MCF7 and T47D) and uterine cancer cells (ECC1 and Ishikawa) through ChIP-Seq and microarray techniques. Surprisingly, we identified large scale differences in the numbers of ERBS between these cell lines when treated with E2 (17-M-NM-2 estradiol). Besides identification of common and unique ERBS between breast and uterine cancer cell types., our data also suggest that both cell types could recruit a large set of common co-operating transcription factors (Co-TFs) and a few unique Co-TFs as well. Besides the genes that are commonly regulatedM-BM- between the different cell lines, there are a number of genes that are differentially regulated in different cell types. Gene pathway analyses of E2 target genes suggest that ER regulates many biological pathways and processes in both tissue-type dependent and independent manners. Our results showed that cell lines derived from same tissue display a greater similarity for both profiles of ERBS and gene expression, and that the differential profiles of ER and preferential recruitment of some Co-TFs are the main determinants for the differential regulation of E2 signaling in breast and uterine cancer cells. In order to explore common and distinctive features of ERM-NM-1 (estrogen receptor alpha) binding profiles between breast and uterus, we generated eight ChIP-Seq libraries for the four cell lines (MCF7, T47D, ECC1 and Ishikawa) under two different treatments (E2, ethanol). In addition, we generated four control libraries for the four cell lines. For all treatment libraries, we generated about 7-12 million unique tags each. ER antibody catalog number is (Santa Cruz,sc-543).

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Effects of Estrogen and Tamoxifen on Ishikawa cells after 24h and 48h

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