Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Insights into the proliferation and invasiveness of breast cancer from genome-wide profiling of estrogen receptor beta 2

ABSTRACT: The human ERβ variant, ERβ2, is expressed at higher levels than ERβ1 in many breast cancer cell lines and breast tumours and increasing evidence supports the hypothesis that ERβ2, in contrast to ERβ1, is associated with aggressive phenotypes of various cancers. We identified a breast cancer cell line that expresses endogenous ERβ2, but not ERα or ERβ1, allowing studies of ERβ2 in the absence of other ER isoforms. Importantly, we show that knockdown of endogenous ERβ2 inhibited cell proliferation and cell invasion. To gain insights into the molecular mechanism responsible for these cellular phenotypes, we assayed ERβ2 dependent global gene expression profiles. A total of 263 genes were identified as potentially ERβ2-upregulated genes and 662 as ERβ2-downregulated genes. ERβ2-regulated genes were involved in cell morphology, DNA replication and repair, cell death and survival. Our findings demonstrate that ERβ2 alone has a key role in enhancing cell proliferation and invasion, beyond modulation of ERα and ERβ1 signalling. BT549 cells grown in antibiotic free medium were transfected with a control siRNA, siRNA targeting ERβ2, ERβ2 cDNA, empty vector control, and then global gene expression profiles were assessed. Three biological replicates were used for each group.

ORGANISM(S): Homo sapiens

SUBMITTER: Li Xu

PROVIDER: E-GEOD-57379 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. In this study, we identify a nuclear hormone receptor (ERα)-protein kinase (ERK5)-cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small molecule inhibitors of ERK5 and MEK5, we show that hormone activation of estrogen receptor-α determines the nuclear versus cytoplasmic localization of the MAPK family member ERK5, which functions as a coregulator of ERα-gene transcription. Notably, ERK5 works with the actin remodeling protein, CFL1, and upon hormone exposure both became localized to transcription factories in the nucleus, verified by immunofluorescence and proximity ligation assays. Both factors facilitated PAF1 recruitment to the RNA Pol II complex and both ERK5 and CFL1 were required for regulation of gene transcription. By contrast, in cells lacking ERα, ERK5 and CFL1 localized to cytoplasmic membrane regions of high actin remodeling, promoting cell motility and invasion, thereby revealing a mechanism likely to contribute to the generally poorer prognosis of ERα-negative breast cancers. Our study uncovers the dynamic interplay of nuclear receptor-mediated transcription and actin reorganization in phenotypes of breast cancer aggressiveness, and highlights new prognostic biomarkers and suggests novel approaches for developing targeted therapies to moderate cancer aggressiveness. MCF-7 human breast adenocarcinoma cells were tranfected with control, and ERK5 siRNA for 72 hours and treated with 0.1% EtOH (Vehicle) or 10 nM E2 for 24 hours, and cDNA microarray analyses were carried out using Affymetrix [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array. siRNA knock-down, ligand treatment

Dataset Information

Insights into the proliferation and invasiveness of breast cancer from genome-wide profiling of estrogen receptor beta 2

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure