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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-4-19
pubmed:abstractText
Staurosporine is a potent apoptosis inducer, but its mechanism remains to be clarified. We investigated the involvement of PTEN in staurosporine-induced apoptosis. Ishikawa cells, from an endometrial carcinoma cell line, expressed a high amount of PTEN mRNA but did not express the PTEN protein because of protein truncations. We isolated clones expressing the steady-state level of the PTEN protein from PTEN-null Ishikawa cells by transfection. The obtained clones showed reduced proliferative activity and reduced anchorage-independent cell growth with the augmented p27(Kip1). These cell lines were sensitized to apoptosis by staurosporine. A low concentration of UCN-01 did not affect apoptosis, but a high concentration augmented apoptosis in the PTEN-expressing clone. Alpha-sphingosine and H-7 did not affect apoptosis in these cell lines. PI3K inhibition augmented staurosporine-induced apoptosis in the parental cell line, but not in the PTEN-expressing clone. In the clone, phosho-Akt/PKB and phospho-Bad (Ser-136) were downregulated. Staurosporine reduced the levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in all the cell lines, but the reduction was most significant in the PTEN-expressing clone. These results suggest that inhibition of the PI3K/Akt/PKB signaling pathway might be associated with staurosporine-induced apoptosis in Ishikawa cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1350-9047
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
414-20
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11965494-Animals, pubmed-meshheading:11965494-Antineoplastic Agents, pubmed-meshheading:11965494-Apoptosis, pubmed-meshheading:11965494-Carcinoma, pubmed-meshheading:11965494-Cells, Cultured, pubmed-meshheading:11965494-Clone Cells, pubmed-meshheading:11965494-Down-Regulation, pubmed-meshheading:11965494-Endometrial Neoplasms, pubmed-meshheading:11965494-Female, pubmed-meshheading:11965494-Mutation, pubmed-meshheading:11965494-PTEN Phosphohydrolase, pubmed-meshheading:11965494-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11965494-Phosphoric Monoester Hydrolases, pubmed-meshheading:11965494-Protein-Serine-Threonine Kinases, pubmed-meshheading:11965494-Proto-Oncogene Proteins, pubmed-meshheading:11965494-Proto-Oncogene Proteins c-akt, pubmed-meshheading:11965494-Signal Transduction, pubmed-meshheading:11965494-Staurosporine, pubmed-meshheading:11965494-Transfection, pubmed-meshheading:11965494-Tumor Cells, Cultured, pubmed-meshheading:11965494-Tumor Suppressor Proteins
pubmed:year
2002
pubmed:articleTitle
PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway.
pubmed:affiliation
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu, 500-8705, Japan.
pubmed:publicationType
Journal Article