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Tamoxifen transcriptional regulation in human mammary epithelial and endometrial stromal cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106892 | GEO | 2018/11/01

REPOSITORIES: GEO

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Tamoxifen transcriptional regulation in human mammary epithelial and endometrial stromal cells

Project description:Tamoxifen transcriptional regulation in human mammary epithelial and endometrial stromal cells

| PRJNA418328 | ENA

Tamoxifen transcriptional regulation in human endometrial stromal cells (HESC)

Project description:Tamoxifen (TAM), used for adjuvant therapy of breast cancer, also increases the risk of endometrial cancer. To compare TAM-induced transcriptional changes we examined human and monkey uterus, as well as cultured normal human mammary epithelial cells (NHMECs) and human endometrial stromal cells (HESCs). Uterine DNA from TAM-exposed women (n=15) and monkeys (Erythrocebus patas n=5, and Macaca fascicularis n=12) showed no difference in 5-methyl-cytosine (5-meC) levels compared to unexposed controls. Studies comparing NHMECs and HESCs exposed to 10 µM TAM for 48 hr showed cell-specific differences by microarray, with confirmation by RT-PCR. In TAM-exposed NHMECs there was significant up-regulation of interferon signaling and immune response pathways, while the TAM-exposed HESCs showed significant up-regulation of steroid and fatty acid biosynthesis pathways. Promoter region CpG islands of several genes highly up-regulated by TAM in each cell type (NHMECs: MX1 and STAT1; HESCs: PPARG, SREBF2, HMCGS and Prune2), were examined for 5-meC, but the levels (≤ 7%), were too low to measure accurately. We also examined several histone H3 lysine dimethylases by Western blot, and showed a significant depletion of total H3 histone, H3K4, H3K27 and H3K36 in TAM-exposed HESCs, with similar but non-significant changes in TAM-exposed NHMECs. Whereas TAM exposure had no discernible effect on 5-meC levels in primate uterus, TAM exposure induced up-regulation of different transcriptional pathways in NHMECs and HESCs, and concomitantly depleted H3 histone lysine dimethylase levels. Therefore, transcriptional dysregulation by TAM, including reduction of histone H3 dimethylase levels, may be related to TAM-induced endometrial carcinogenesis.

2018-11-01 | GSE106890 | GEO

Genome-wide analysis of histone modifications in human endometrial stromal cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-03-03 | E-GEOD-57010 | biostudies-arrayexpress

Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-09-07 | E-GEOD-47361 | biostudies-arrayexpress

Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-03-31 | E-GEOD-46285 | biostudies-arrayexpress

PDEF knockdown and overexpression in mammary epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-03-29 | E-GEOD-40987 | biostudies-arrayexpress

Tamoxifen transcriptional regulation in human endometrial stromal cells (HESC)

Project description:Tamoxifen transcriptional regulation in human endometrial stromal cells (HESC)

| PRJNA418377 | ENA

Tamoxifen transcriptional regulation in normal human mammary epithelial cells (NHMEC)

2018-11-01 | GSE106891 | GEO

Tamoxifen-associated endometrial tumors expose differential enhancer activity for Estrogen Receptor alpha

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-07 | GSE94524 | GEO

Early parity-induced gene expression in total mammary epithelial cells and mammary cell subtypes in mice

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-03-17 | E-GEOD-40877 | biostudies-arrayexpress

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