Document Detail


The Akt pathway in human breast cancer: a tissue-array-based analysis.
MedLine Citation:
PMID:  16341149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Akt pathway, an important regulator of cell proliferation and survival, is deregulated in many cancers. The pathway has achieved considerable importance due to the development of kinase inhibitors that are able to successfully reduce tumor growth. This study was conducted to determine the status of the Akt pathway in human breast cancers and to study the relationship between the different component proteins. Expression levels of PTEN, phosphorylated forms of the constituent proteins (Akt, FKHR, mTOR, and S6) and cyclin D1 were evaluated by immunohistochemistry, on consecutive sections from a tissue microarray containing 145 invasive breast cancers and 140 pure ductal carcinomas in-situ. Aberrant expression was correlated statistically with tumor characteristics and disease outcome. The Akt pathway was found to be activated early in breast cancer, in the in-situ stage. In all, 33, 15, 32, and 60% of ductal carcinoma in-situ showed overexpression of Akt, FKHR, mTOR, and cyclin D1. PTEN loss did not correlate statistically with expression of AKT or any of the other proteins with the exception of S6, indicating that Akt activation was not a result of PTEN loss. Expression levels of PTEN and S6 were significantly different in in-situ and invasive cancers, indicating association with disease progression. Loss of PTEN was noted in 11% of in-situ as compared to 26% of invasive cancers, while S6 overexpression was seen in 47% in-situ and in 72% invasive cancers. High-grade carcinomas were associated with PTEN loss, while low-grade carcinomas with good prognostic features showed cyclin D1 overexpression and were associated with longer disease free survival. Additionally, cancers with mTOR overexpression showed a three times greater risk for disease recurrence. Overall, a large proportion of in-situ and invasive breast cancers overexpressed cyclinD1 and S6. Our results may have significant implications in the development and application of targeted therapy.
Authors:
Shikha Bose; Sindhu Chandran; James M Mirocha; Namrata Bose
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  19     ISSN:  0893-3952     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-20     Completed Date:  2006-03-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  238-45     Citation Subset:  IM    
Affiliation:
Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. BoseS@cshs.org
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / metabolism,  pathology*,  physiopathology
Carcinoma, Intraductal, Noninfiltrating / metabolism,  pathology,  physiopathology
Cyclin D1 / analysis
Disease Progression
Female
Humans
Immunohistochemistry
Logistic Models
Multivariate Analysis
Neoplasm Invasiveness
PTEN Phosphohydrolase / analysis
Protein Kinases / analysis
Proto-Oncogene Proteins c-akt / analysis,  physiology*
Ribosomal Protein S6 Kinases / analysis
Signal Transduction*
Survival Analysis
Tissue Array Analysis / methods
Chemical
Reg. No./Substance:
136601-57-5/Cyclin D1; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase

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


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