Linked Life Data

20861921

Source:http://linkedlifedata.com/resource/pubmed/id/20861921

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-15
pubmed:abstractText
The PI3K/Akt pathway is activated in response to various microenvironmental stimuli that regulate the survival and proliferation of chronic lymphocytic leukemia (CLL) B-cells, including triggering of the B-cell receptor (BCR). Although this pathway is frequently targeted in cancer, no significant alterations have yet been identified in CLL. We now show that the phosphatase PH domain leucin-rich repeat protein phosphatase (PHLPP1), a recently identified tumor suppressor and negative regulator of the Akt kinase, is absent or expressed at substantially reduced levels in CLL B-cells. To determine what the consequences of PHLPP1 loss on BCR signaling are, we downregulated or re-expressed PHLPP1 in lymphoma cell lines and primary CLL B-cells, respectively. Downregulation of PHLPP1 increased BCR-induced phosphorylation and activation of the Akt, GSK3 and ERK kinases, whereas re-expression had the opposite effect. Importantly, re-expression of PHLPP1 in primary CLL cells prevented upregulation of Mcl-1 and inhibited the increase in leukemic cell viability induced by sustained BCR engagement. Enforced expression of PHLPP1 also affected the response to other microenvironmental stimuli, particularly in terms of ERK phosphorylation. Collectively, these data show that CLL cells lack an important negative regulator of the Akt and ERK pathways, which could confer them a growth advantage by facilitating the propagation of crucial microenvironment-derived stimuli.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1476-5551
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2063-71
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Reduced expression of the tumor suppressor PHLPP1 enhances the antiapoptotic B-cell receptor signal in chronic lymphocytic leukemia B-cells.
pubmed:affiliation
Department of Molecular Hematology, ICGEB, Campus Adriano Buzzati-Traverso, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't