Document Detail


PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway.
MedLine Citation:
PMID:  11965494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
X Wan; Y Yokoyama; A Shinohara; Y Takahashi; T Tamaya
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell death and differentiation     Volume:  9     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-19     Completed Date:  2002-08-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  414-20     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu, 500-8705, Japan.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Carcinoma / enzymology*,  pathology
Cells, Cultured
Clone Cells
Down-Regulation
Endometrial Neoplasms / enzymology*,  pathology
Female
Mutation
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases / genetics,  metabolism,  physiology*
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Signal Transduction
Staurosporine / pharmacology*
Transfection
Tumor Cells, Cultured
Tumor Suppressor Proteins / genetics,  metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 62996-74-1/Staurosporine; EC 2.7.1.-/3-phosphoinositide-dependent protein kinase; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.67/PTEN Phosphohydrolase

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