Linked Life Data

20028853

Source:http://linkedlifedata.com/resource/pubmed/id/20028853

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-5
pubmed:abstractText
Activation of the beta-catenin and receptor kinase pathways occurs often in medulloblastoma, the most common pediatric malignant brain tumor. In this study, we show that molecular cross-talk between the beta-catenin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways is crucial to sustain medulloblastoma pathophysiology. Constitutive activation of phosphoinositide-dependent protein kinase 1 (PDK1), Akt, and phosphorylation of [corrected] glycogen synthase kinase 3beta (GSK-3beta) was detected by immunohistochemistry in all primary medulloblastomas examined (n = 41). Small-molecule inhibitors targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc. The PDK1 inhibitor OSU03012 induced mitochondrial-dependent apoptosis of medulloblastoma cells and enhanced the cytotoxic effects of chemotherapeutic drugs in a synergistic or additive manner. In vivo, OSU03012 inhibited the growth of established medulloblastoma xenograft tumors in a dose-dependent manner and augmented the antitumor effects of mammalian target of rapamycin inhibitor CCI-779. These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt signaling pathway as a therapeutic target in treatment of this disease.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
266-76
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20028853-Animals, pubmed-meshheading:20028853-Antineoplastic Agents, pubmed-meshheading:20028853-Cerebellar Neoplasms, pubmed-meshheading:20028853-Flow Cytometry, pubmed-meshheading:20028853-Fluorescent Antibody Technique, pubmed-meshheading:20028853-Humans, pubmed-meshheading:20028853-Immunohistochemistry, pubmed-meshheading:20028853-Medulloblastoma, pubmed-meshheading:20028853-Mice, pubmed-meshheading:20028853-Phosphatidylinositol 3-Kinases, pubmed-meshheading:20028853-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20028853-RNA, Small Interfering, pubmed-meshheading:20028853-Receptor Cross-Talk, pubmed-meshheading:20028853-Signal Transduction, pubmed-meshheading:20028853-Sirolimus, pubmed-meshheading:20028853-Transfection, pubmed-meshheading:20028853-Wnt Proteins, pubmed-meshheading:20028853-Xenograft Model Antitumor Assays, pubmed-meshheading:20028853-beta Catenin
pubmed:year
2010
pubmed:articleTitle
Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth.
pubmed:affiliation
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. ninib.baryawno@ki.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't