Linked Life Data

19435816

Source:http://linkedlifedata.com/resource/pubmed/id/19435816

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-21
pubmed:abstractText
Wild-type p53-induced phosphatase (Wip1) is a serine/threonine phosphatase induced by DNA-damaging agents. This enzyme dephosphorylates several cell cycle regulating proteins, including p53, p38 mitogen-activated protein kinase, Chk1, and Chk2, resulting in negative feedback regulation of p38-p53 signaling after damage repair. Moreover, the Wip1 gene may be amplified or overexpressed, especially in hormone-regulated organs, and Wip1 gene amplification has been correlated with poor prognosis in hormone-related malignancies, including ovarian cancers. We therefore investigated the link between estrogen signaling and Wip1 expression. We identified seven putative estrogen response elements within 3 kb of the Wip1 promoter. We also found that estradiol (E(2)) treatment produced a 3-fold increase in endogenous Wip1 mRNA and protein expression in MCF7 cells. Direct binding of estrogen receptor (ER)alpha to the Wip1 promoter after E(2) treatment was confirmed by a chromatin immunoprecipitation assay using ERalpha antibody and an electrophoretic mobility shift assay. Wip1 overexpression induced by adenovirus and E(2) facilitated the proliferation of serum-starved ZR-75-1 cells, with cell proliferation induced by overexpressed Wip1 approximately 25% higher than that induced by E(2). Wip1 phosphatase activity was essential for cell cycle progression. Wip1 stimulated the transcriptional activity of its own promoter through E(2)-ERalpha signaling. In addition, Wip1 overexpression induced Rb phosphorylation during cancer cell proliferation. These results indicate that Wip1 up-regulation is important in the pathogenesis of p53(+) and ER(+) breast cancer through the inactivation of p53 by dephosphorylation and the amplification of subsequent estrogenic effects through the E(2)-ERalpha-Wip1 pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
713-23
pubmed:meshHeading
pubmed-meshheading:19435816-Base Sequence, pubmed-meshheading:19435816-Binding Sites, pubmed-meshheading:19435816-Blotting, Western, pubmed-meshheading:19435816-Breast Neoplasms, pubmed-meshheading:19435816-Cell Cycle, pubmed-meshheading:19435816-Cell Line, Tumor, pubmed-meshheading:19435816-Electrophoretic Mobility Shift Assay, pubmed-meshheading:19435816-Estrogen Receptor alpha, pubmed-meshheading:19435816-Estrogens, pubmed-meshheading:19435816-Female, pubmed-meshheading:19435816-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19435816-HCT116 Cells, pubmed-meshheading:19435816-Humans, pubmed-meshheading:19435816-Models, Biological, pubmed-meshheading:19435816-Phosphoprotein Phosphatases, pubmed-meshheading:19435816-Phosphorylation, pubmed-meshheading:19435816-Plasmids, pubmed-meshheading:19435816-Promoter Regions, Genetic, pubmed-meshheading:19435816-Protein Binding, pubmed-meshheading:19435816-Response Elements, pubmed-meshheading:19435816-Retinoblastoma Protein, pubmed-meshheading:19435816-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19435816-Signal Transduction, pubmed-meshheading:19435816-Transfection, pubmed-meshheading:19435816-Tumor Suppressor Protein p53
pubmed:year
2009
pubmed:articleTitle
The estrogen receptor alpha pathway induces oncogenic Wip1 phosphatase gene expression.
pubmed:affiliation
Department of Pathology, University of Ulsan College of Medicine, 388-1 Pungnap-2 dong, Songpa-gu, Seoul 138-736, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't