Linked Life Data

18212741

Source:http://linkedlifedata.com/resource/pubmed/id/18212741

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2008-6-5
pubmed:abstractText
Glioblastoma multiforme is the most aggressive form of primary brain tumor and remains largely incurable, in large part, due to its highly invasive nature. The phosphoinositide (PI) 3-kinase pathway is often constitutively active in these tumors due to activating mutations in the epidermal growth factor receptor, or deletion/loss of function of the tumor suppressor PTEN. Protein kinase C type iota (PKC iota), a member of the atypical protein kinase C family, is activated by the PI 3-kinase pathway and is an important downstream mediator. Here, we have assessed the role of PKC iota in glioblastoma cell invasion. Depletion of PKC iota with RNA interference caused an increase in actin stress fibers and a decrease in cell motility and invasion. Gene expression microarray analysis of U87MG cells showed that PKC iota repressed expression of mRNA for RhoB, which has previously been shown to have a role in actin stress fiber formation. Western blot analysis showed that both PKC iota depletion and pharmacological inhibition of PKC iota caused an increase in the protein levels of RhoB, as did inhibition of PI 3-kinase. Expression of RhoB from a constitutive promoter caused changes in actin stress fibers and cell invasion that were similar to those seen with PKC iota depletion. These data show that PKC iota, activated as a consequence of aberrant upstream PI 3-kinase signaling, mediates glioblastoma cell motility and invasion, and that repression of RhoB is key downstream event in PKC iota signaling leading to enhanced cell motility. In addition, constitutive expression of RhoB repressed PKC iota activity, as assessed by its phosphorylation status on Thr555. PKC iota and RhoB are, therefore, mutually antagonistic, potentially creating a sensitive switch between invasive and non-invasive phenotypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3587-95
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18212741-Brain Neoplasms, pubmed-meshheading:18212741-Cell Line, Tumor, pubmed-meshheading:18212741-Cell Movement, pubmed-meshheading:18212741-Gene Expression Profiling, pubmed-meshheading:18212741-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18212741-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18212741-Glioblastoma, pubmed-meshheading:18212741-Humans, pubmed-meshheading:18212741-Isoenzymes, pubmed-meshheading:18212741-Models, Biological, pubmed-meshheading:18212741-Neoplasm Invasiveness, pubmed-meshheading:18212741-Phosphatidylinositol 3-Kinases, pubmed-meshheading:18212741-Promoter Regions, Genetic, pubmed-meshheading:18212741-Protein Kinase C, pubmed-meshheading:18212741-RNA Interference, pubmed-meshheading:18212741-rhoB GTP-Binding Protein
pubmed:year
2008
pubmed:articleTitle
Regulation of glioblastoma cell invasion by PKC iota and RhoB.
pubmed:affiliation
Ottawa Health Research Institute, Ottawa, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't