Genes targeted by the estrogen and progesterone receptors in the human endometrial cell lines HEC1A and RL95-2

Abstract

BackgroundWhen the steroid hormones estrogen and progesterone bind to nuclear receptors, they have transcriptional impact on target genes in the human endometrium. These transcriptional changes have a critical function in preparing the endometrium for embryo implantation.Methods382 genes were selected, differentially expressed in the receptive endometrium, to study their responsiveness of estrogen and progesterone. The endometrial cell lines HEC1A and RL95-2 were used as experimental models for the non-receptive and receptive endometrium, respectively. Putative targets for activated steroid hormone receptors were investigated by chromatin immunoprecipitation (ChIP) using receptor-specific antibodies. Promoter occupancy of the selected genes by steroid receptors was detected in ChIP-purified DNA by quantitative PCR (qPCR). Expression analysis by reverse transcriptase (RT)-PCR was used to further investigate hormone dependent mRNA expression regulation of a subset of genes.ResultsChIP-qPCR analysis demonstrated that each steroid hormone receptor had distinct group of target genes in the endometrial cell lines. After estradiol treatment, expression of estrogen receptor target genes predominated in HEC1A cells (n = 137) compared to RL95-2 cells (n = 35). In contrast, expression of progesterone receptor target genes was higher in RL95-2 cells (n = 83) than in HEC1A cells (n = 7) after progesterone treatment. RT-PCR analysis of 20 genes demonstrated transcriptional changes after estradiol or progesterone treatment of the cell lines.ConclusionsCombined results from ChIP-qPCR and RT-PCR analysis showed different patterns of steroid hormone receptor occupancy at target genes, corresponding to activation or suppression of gene expression after hormone treatment of HEC1A and RL95-2 cell lines.

The Tissue Specific Role of Estrogen and Progesterone in Human Endometrium and Mammary Gland

“…We found 137 target genes for ERs in HEC1A and 83 target genes for PRs in RL95-2 from 382 preselected genes. The results confirmed the in vitro model of non-receptive (HEC1A) and receptive (RL95-2) endometrium in steroid hormone manner (Tamm et al, 2009). …”

Progesterone Receptor Transcriptome and Cistrome in Decidualized Human Endometrial Stromal Cells

“…Response to wounding (GO: 0009611) TPST1, MASP1, TNC, STAT5B, COL3A1, AFAP1L2, TLR4, C1R, ITGB3, C1S, ELK3, LMAN1, TPM1, TNFRSF1B, HMCN1, NOD1, CTGF, SCARB1, THBS1, NRG1, NOX4, PLAT, KLF6, LIPA, TNFSF4, PDPN, MAP1B, ITGA2, COL5A1, STAT3, HDAC4, PLSCR1, PLSCR4, F3, PDGFRA, C1RL, TFPI, NFE2L1, VCAN, JAK2 PGR are genes known to be direct targets of PGR in human endometrial cell and in the murine endometrium, including FKBP5, HAND2, CYR61, ETS translocation variant 1 (ETV1), collagen ␣-1 (XV) chain (COL15A1), vascular endothelial growth factor receptor 1 (FLT1), and monoamine oxidase A (MAOA) (22,48). PGR has been shown to bind and activate the promoters of IGFBP1 and PRL in luciferase reporter assays (31,49).…”

Role of estrogen receptor β in gynecological cancer

“…Human endometrium is a dynamic tissue that undergoes cyclic changes in preparation for receptivity and embryo implantation, predominantly regulated by ovarian steroids [47,48]. In western countries, endometrial cancer is the most common cancer type of the female genital tract [49].…”