Linked Life Data

9931326

Source:http://linkedlifedata.com/resource/pubmed/id/9931326

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-3-18
pubmed:abstractText
PTEN is a novel tumour suppressor gene that encodes a dual-specificity phosphatase with homology to adhesion molecules tensin and auxillin. It recently has been suggested that PTEN dephosphorylates phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3, 4,5)P3], which mediates growth factor-induced activation of intracellular signalling, in particular through the serine-threonine kinase Akt, a known cell survival-promoting factor. PTEN has been mapped to 10q23.3, a region disrupted in several human tumours including haematological malignancies. We have analysed PTEN in a series of primary acute leukaemias and non-Hodgkin's lymphomas (NHLs) as well as in cell lines. We have also examined whether a correlation could be found between PTEN and Akt levels in these samples. We show here that the majority of cell lines studied carries PTEN abnormalities. At the structural level, we found mutations and hemizygous deletions in 40% of these cell lines, while a smaller number of primary haematological malignancies, in particular NHLs, carries PTEN mutations. Moreover, one-third of the cell lines had low PTEN transcript levels, and 60% of these samples had low or absent PTEN protein, which could not be attributed to gene silencing by hypermethylation. In addition, we found that PTEN and phosphorylated Akt levels are inversely correlated in the large majority of the examined samples. These findings suggest that PTEN plays a role in the pathogenesis of haematological malignancies and that it might be inactivated through a wider range of mechanisms than initially considered. The finding that PTEN levels inversely correlate with phosphorylated Akt supports the hypothesis that PTEN regulates PtdIns(3,4,5)P3and suggests a role for PTEN in apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9931326-Blotting, Northern, pubmed-meshheading:9931326-DNA, Neoplasm, pubmed-meshheading:9931326-DNA Mutational Analysis, pubmed-meshheading:9931326-Gene Expression Regulation, Neoplastic, pubmed-meshheading:9931326-HL-60 Cells, pubmed-meshheading:9931326-Hematologic Neoplasms, pubmed-meshheading:9931326-Humans, pubmed-meshheading:9931326-K562 Cells, pubmed-meshheading:9931326-Methylation, pubmed-meshheading:9931326-Mutation, pubmed-meshheading:9931326-Neoplasm Proteins, pubmed-meshheading:9931326-PTEN Phosphohydrolase, pubmed-meshheading:9931326-Phosphoric Monoester Hydrolases, pubmed-meshheading:9931326-Protein-Serine-Threonine Kinases, pubmed-meshheading:9931326-Proto-Oncogene Proteins, pubmed-meshheading:9931326-Proto-Oncogene Proteins c-akt, pubmed-meshheading:9931326-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:9931326-Sequence Deletion, pubmed-meshheading:9931326-Transcription, Genetic, pubmed-meshheading:9931326-Tumor Cells, Cultured, pubmed-meshheading:9931326-Tumor Suppressor Proteins
pubmed:year
1999
pubmed:articleTitle
PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanismsin haematological malignancies.
pubmed:affiliation
Departments of Adult Oncology and Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't