RGD Reference Report - The Akt pathway in human breast cancer: a tissue-array-based analysis. - Rat Genome Database

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The Akt pathway in human breast cancer: a tissue-array-based analysis.

Authors: Bose, S  Chandran, S  Mirocha, JM  Bose, N 
Citation: Bose S, etal., Mod Pathol. 2006 Feb;19(2):238-45.
RGD ID: 1643333
Pubmed: PMID:16341149   (View Abstract at PubMed)
DOI: DOI:10.1038/modpathol.3800525   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AKT1Humanin situ carcinoma  IEP ductal carcinoma in situ and protein:increased phosphorylation:breastRGD 
Akt1Ratin situ carcinoma  ISOAKT1 (Homo sapiens)ductal carcinoma in situ and protein:increased phosphorylation:breastRGD 
Akt1Mousein situ carcinoma  ISOAKT1 (Homo sapiens)ductal carcinoma in situ and protein:increased phosphorylation:breastRGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)

Genes (Mus musculus)
Akt1  (thymoma viral proto-oncogene 1)

Genes (Homo sapiens)
AKT1  (AKT serine/threonine kinase 1)


Additional Information