Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human ER+ BrC cells with and without estradiol in both cell cultures and xenografts

ABSTRACT: We generated DNA microarray based gene expression profiles from three estrogen receptor a (ERa) positive breast cancer cell lines stimulated by 17Ã?-estradiol (E2) in vitro over a time course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic nude mice with E2 supplementation and after its withdrawal. Experiment Overall Design: 8 MCF-7 xenograft profiles (4 with E2,4 without E2), 14 T47D profiles (with E2 treatment in culture from 0 to 24 hr), 10 BT-474 profiles (with E2 treatment from 0 to 24 hr), 12 MCf-7 profiles (with E2 treatment from 0 to 24 hr)

ORGANISM(S): Homo sapiens

SUBMITTER: Chad Creighton

PROVIDER: E-GEOD-3834 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors.

Creighton Chad J CJ Cordero Kevin E KE Larios Jose M JM Miller Rebecca S RS Johnson Michael D MD Chinnaiyan Arul M AM Lippman Marc E ME Rae James M JM

Genome biology 20060407 4

<h4>Background</h4>Estrogen plays a central role in breast cancer pathogenesis. Although many studies have characterized the estrogen regulation of genes using in vitro cell culture models by global mRNA expression profiling, it is not clear whether these genes are similarly regulated in vivo or how they might be coordinately expressed in primary human tumors.<h4>Results</h4>We generated DNA microarray-based gene expression profiles from three estrogen receptor alpha (ERalpha)-positive breast ca ...[more]

PMID: 16606439

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Project description:Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile (i.e presence/absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2, (HER2)). Thus, we explored the androgen-regulated transcriptomic changes in the ER+PR+HER2+ BCa cell line, BT-474, and compared them with PR-mediated changes. Methods: We performed RNA sequencing analysis, in treated BT-474 cells with dihydrotestosterone (DHT) and progesterone (PROG). Validation of the top ten differentially androgen-regulated genes and a number of other genes found in enriched signaling pathways was performed by qRT-PCR in BT-474 and other BCa cell lines. A parallel reaction monitoring targeted proteomic approach was developed for the verification of selected transcripts at the protein level. Results: We detected 19,450 transcripts, of which 224 were differentially regulated after DHT treatment. The increased expression of two well-known androgen-regulated genes, KLK2 (p<0.05) and KLK3 (p<0.001), confirmed the successful androgen stimulation in BT-474 cells. The transcription factor, ZBTB16, was the most highly upregulated gene, with ~1000-fold change (p<0.001). Pathway enrichment analysis revealed downregulation of the DNA replication processes (p<0.05), and upregulation of the androgen signaling and fatty acid metabolism pathways (p<0.05). Changes related to PROG-treatment showed opposite effects in gene expression than DHT treatment. Similar expression profiles were observed among other BCa cell lines expressing high levels of AR (ZR75.1 and MBA-MB-453). The parallel reaction monitoring targeted proteomic analysis further confirmed that altered protein expression (e.g. KLK3, and ALOX15B) in the supernatant and cell lysate of DHT-treated BT-474 cells, compared to control cells. Discussion: Collectively, our findings suggest that AR modulates the metabolism of BT-474 cells by affecting expression of a large number of genes and proteins. Based on further pathway analysis, we suggest that AR acts as a tumor suppressor in BT-474 cells.

Dataset Information

Transcription profiling of human ER+ BrC cells with and without estradiol in both cell cultures and xenografts

Publications

Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors.

Similar Datasets

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