PLK1 signaling coopereates with estrogen receptor-dependent gene transcription
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Wierer Michael
PROVIDER: S-ECPF-GEOD-46856 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Analysis of MCF7 breast cancer cells treated with estadiol for 6 h in presence or absence of the specific PLK1 inhibitor BI2536. Together with CHIP and global phosphoproteome data, the results demonstrate a key role of PLK1 in the estrogen receptor-mediated gene response. Hormone-deprived MCF7 cells were pretreated with BI2536 or vehicle (DMSO) followed by induction with estradiol (E2) or vehicle (ethanol). RNA of each condition was analysed in triplicate on an Agilent Human genome 4x44k v2 microarray [note: MCF7_DMSO_E2_rep3 sample was a clear technical outlier (poor hybridization), and was therefore excluded from the further analysis/this record].
2014-01-01 | E-GEOD-46856 | biostudies-arrayexpress
Project description:Analysis of MCF7 breast cancer cells treated with estadiol for 6 h in presence or absence of the specific PLK1 inhibitor BI2536. Together with CHIP and global phosphoproteome data, the results demonstrate a key role of PLK1 in the estrogen receptor-mediated gene response.
2014-01-01 | GSE46856 | GEO
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Project description:Estrogen receptor-alpha (ERalpha) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERalpha mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERalpha knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERalpha that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERalpha pathways. Surprisingly, we found that ligand-independent ERalpha signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERalpha signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERalpha knock-in (ENERKI) mice with the ERalpha selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERalpha in vivo, we discovered male fertility required neonatal estrogen-mediated ERalpha signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERalpha in human infertility should be examined more closely.
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Project description:17?-estradiol (E2), the primary circulating estrogen hormone, mediates physiological and pathophysiological functions of breast tissue mainly through estrogen receptor ? (ER?). Upon binding to E2, ER? modulates the expression of target genes involved in the regulation of cellular proliferation primarily through interactions with specific DNA sequences, estrogen response elements (EREs). Our previous microarray results suggested that E2-ER? modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds to non-methylated CpG dinucleotides. Although studies are limited, CXXC5 appears to participate as a transcription factor, co-regulator and/or epigenetic factor in the regulation of cellular events induced by various signaling pathways. However, how signaling pathways mediate the expression of CXXC5 is yet unclear. Due to the importance of E2-ER? signaling in breast tissue, changes in the CXXC5 transcription/synthesis could participate in E2-mediated cellular events as well. To address these issues, we initially examined the mechanism whereby E2-ER? regulates CXXC5 expression. We show here that CXXC5 is an E2-ER? responsive gene regulated by the interaction of E2-ER? with an ERE present at a region upstream of the initial translation codon of the gene.
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