Document Detail

Growth and activation of PI-3K/PKB and Akt by stromal cell-derived factor 1alpha in endometrial carcinoma cells with expression of suppressor endoprotein PTEN.
MedLine Citation:
PMID:  16542580     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Mutation or deletion in the phosphatase and tensin homologue deleted on chromosome ten (PTEN) gene has been identified as an important cause of endometrial carcinoma; stromal cell derived factor-1alpha (SDF-1alpha) exerts growth-promoting effects on endometrial cancer cells through activation of the PI-3 kinase/Akt pathway and downstream effectors such as extracellular-responsive kinase (ERK). In this study, a plasmid containing the PTEN gene was transfected into Ishikawa cells to investigate the difference in growth and signal transduction between Ishikawa-PTEN and Ishikawa cells after SDF-1alpha stimulation, and to study mechanisms of the involvement of PTEN protein in endometrial carcinoma development. METHODS: Ishikawa cells were transfected with a plasmid (pLXSN-PTEN) containing the PTEN gene and a plasmid (pLXSN-EGFP) with enhanced green fluorescent protein (EGFP). Cells were then screened to obtain Ishikawa-PTEN cells and Ishikawa-neo cells that can both stably express PTEN protein and EGFP. Expression of PTEN protein, phosphorylation levels of AKT and ERK (pAKT and pERK) and growth differences in Ishikawa-PTEN, Ishikawa-neo and Ishikawa cells before and after SDF-1alpha stimulation were then determined by Western blots and MTT assays. RESULTS: Western blot analysis showed that Ishikawa cells produced PTEN after transfection with the PTEN gene. At 15 minutes after SDF-1alpha stimulation, the pAKT level of Ishikawa-PTEN cells was lower than that of Ishikawa-neo cells and Ishikawa cells. There was no significant difference in pERK levels among the three cell lines. The positive effect of SDF-1alpha on Ishikawa-PTEN cells growth was markedly less than the effect on Ishikawa-neo and Ishikawa cells. However, in the absence of SDF-1alpha stimulation (baseline), the pAKT level in Ishikawa-PTEN cells was less than that in Ishikawa cells. There was a significant difference in growth between the Ishikawa-PTEN cells and the Ishikawa-neo cells. CONCLUSIONS: PTEN gene transfection can regulate the level of pAKT but not pERK in Ishikawa-PTEN cells. PTEN protein may suppress the growth-promoting effect of SDF-1alpha on endometrial carcinoma by inhibiting the PI-3K/AKT signal transduction pathway.
Xiao-ping Li; Dan Zhao; Min Gao; Chao Zhao; Jian-liu Wang; Li-hui Wei
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chinese medical journal     Volume:  119     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-17     Completed Date:  2006-04-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  378-83     Citation Subset:  IM    
Gynecological Oncology Center, Peking University People's Hospital, Beijing 100044, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
1-Phosphatidylinositol 3-Kinase / physiology*
Cell Line, Tumor
Cell Proliferation / drug effects
Chemokine CXCL12
Chemokines, CXC / pharmacology*
Endometrial Neoplasms / pathology*
PTEN Phosphohydrolase / physiology*
Proto-Oncogene Proteins c-akt / physiology*
Signal Transduction
Reg. No./Substance:
0/CXCL12 protein, human; 0/Chemokine CXCL12; 0/Chemokines, CXC; EC 3-Kinase; EC Proteins c-akt; EC protein, human; EC Phosphohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome.
Next Document:  Inhibitory effects of polymyxin B on NF-kappaB activation and expression of procollagen I, III in pr...