Document Detail


Co-existence of high levels of the PTEN protein with enhanced Akt activation in renal cell carcinoma.
MedLine Citation:
PMID:  17681738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recruiting Akt to the membrane-bound phosphatidylinositol (3,4,5) trisphosphate (PIP3) is required for Akt activation. While PI3 kinase (PI3K) produces PIP3, PTEN dephosphorylates the 3-position phosphate from PIP3, thereby directly inhibiting Akt activation. PTEN is the dominant PIP3 phosphatase, as knockdown of PTEN results in increases in Akt activation in mice. The PTEN tumor suppressor gene is frequently mutated in a variety of human cancers, consistent with an inverse correlation between levels of the PTEN protein and Akt activation. We have examined PTEN expression and Akt activation in 35 primary clear cell renal cell carcinomas RCCs (ccRCCs) and 9 papillary RCCs (pRCCs) and their respective non-tumor kidney tissues. The PTEN protein was reduced in 16 ccRCCs (16/35=45.7%) and 8 pRCCs (8/9=88.9%). In these RCCs, 25.0% (4/16) of ccRCCs and 25.0% (2/8) of pRCCs expressed elevated Akt activation. 19 ccRCCc (19/35=54.3%) expressed comparable or higher levels of PTEN. Of these ccRCCs, 31.6% (6/19) showed increases in Akt activation. As PTEN dominantly inhibits Akt activation, the coexistence of high levels of the PTEN protein with enhanced Akt activation suggests the existence of novel mechanisms which attenuate PTEN function in ccRCC. These mechanisms may reduce PTEN function or increase PIP3 production.
Authors:
Lizhi He; Catherine Fan; Aubrey Gillis; Xinchang Feng; Michael Sanatani; Sebastien Hotte; Anil Kapoor; Damu Tang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-12
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1772     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-12-07     Completed Date:  2008-02-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1134-42     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Department of Medicine, McMaster University, and Father Sean O'Sullivan Research Centre, St. Joseph's Hospital, 50 Charlton Ave East, Hamilton, ON, Canada L8N 4A6.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Animals
Carcinoma, Papillary / enzymology*,  pathology
Carcinoma, Renal Cell / enzymology*,  pathology
Enzyme Activation
Humans
Kidney Neoplasms / enzymology*,  pathology
Mice
PTEN Phosphohydrolase / metabolism*
Phosphatidylinositol Phosphates / metabolism
Proto-Oncogene Proteins c-akt / metabolism*
Chemical
Reg. No./Substance:
0/Phosphatidylinositol Phosphates; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase

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