Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data for Control and SMRT-Depleted MCF-7 Cells

ABSTRACT: Estrogens are an important regulator of breast cancer disease progression, and they function by binding the estrogen receptor--alpha (ER-alpha) to regulate changes in gene expression. ER-alpha is able to both activate and inhibit gene transcription in a gene-specific manner and do so by binding target DNA sequences and recruiting coactivators and corepressors which can modulate the chromatin environment. Silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) is known to act as coactivator and corepressor of ER-alpha in a gene-specific manner. We used a microarray analysis to examine the gene expression changes that occur when the coregulator SMRT is depleted from the ER-alpha positive MCF-7 breast cancer cell line. We sought to determine the genes that are regulated by depletion of the coregulator SMRT using Affymetrix Human Gene 1.0 ST Array. To this end, we transfected MCF-7 cells with control siRNA or SMRT-targeting siRNA for 48 h and treated for an additional 4 or 24 h with vehicle (0.1% EtOH) or 1 nM estradiol (E2). A total of 24 samples were analyzed, separated into eight groups each with three experimental replicates in each group, siControl-Veh 4 h, siControl -E2 4 h, siSMRT-Veh 4 h, siSMRT-E2 4 h, siControl-Veh 24 h, siControl-E2 24 h, siSMRT-Veh 24 h, siSMRT-E2 24 h.

ORGANISM(S): Homo sapiens

SUBMITTER: Carolyn Smith

PROVIDER: E-GEOD-57935 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The SMRT coregulator enhances growth of estrogen receptor-α-positive breast cancer cells by promotion of cell cycle progression and inhibition of apoptosis.

Blackmore Julia K JK Karmakar Sudipan S Gu Guowei G Chaubal Vaishali V Wang Liguo L Li Wei W Smith Carolyn L CL

Endocrinology 20140627 9

The SMRT coregulator functions as a dual coactivator and corepressor for estrogen receptor-α (ERα) in a gene-specific manner, and in several studies its elevated expression correlates with poor outcome for breast cancer patients. A specific role of SMRT in breast cancer progression has not been elucidated, but SMRT knock-down limits estradiol-dependent growth of MCF-7 breast cancer cells. In this study, small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) approaches were used to determine ...[more]

PMID: 24971610

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Project description:Estrogen receptorï? beta (ER beta) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER beta-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER beta regulates genes, we identified genes regulated by the unliganded and liganded forms of ER alpha and ER beta in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER alpha, whereas many genes were regulated by estradiol (E2). These results demonstrate ER alpha requires a ligand to regulate a single class of genes. In contrast, ER beta regulated three classes of genes. Class I genes were regulated primarily by unliganded ER beta. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER beta and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER beta regulates different classes of genes ChIP-seq was performed to identify ER beta binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER beta bound to all three classes of genes demonstrating that ER beta binding is not responsible for differential regulation of genes by unliganded and liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators. U2OS cell lines are stably transfected with a doxycycline-inducible ER alpha or beta. 18 samples are analyzed with triplicate for each of the 6 conditions. The 6 conditions include ER alpha transfected without doxycycline added, ER alpha transfected with doxycycline added, ER alpha transfected with doxycycline added and E2 treatment, ER beta transfected without doxycycline added, ER beta transfected with doxycycline added, and ER beta transfected with doxycycline added and E2 treatment.

Dataset Information

Expression data for Control and SMRT-Depleted MCF-7 Cells

Publications

The SMRT coregulator enhances growth of estrogen receptor-α-positive breast cancer cells by promotion of cell cycle progression and inhibition of apoptosis.

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