RGD Reference Report - Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor. - Rat Genome Database

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Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor.

Authors: Hara, S  Oya, M  Mizuno, R  Horiguchi, A  Marumo, K  Murai, M 
Citation: Hara S, etal., Ann Oncol. 2005 Jun;16(6):928-33. Epub 2005 Apr 25.
RGD ID: 2292677
Pubmed: PMID:15851405   (View Abstract at PubMed)
DOI: DOI:10.1093/annonc/mdi182   (Journal Full-text)

BACKGROUND: Akt has been implicated in the oncogenesis of human malignant tumors, because Akt regulates many key effector molecules involved in cell survival. PTEN (phosphatase and tensin homolog deleted on chromosome 10) negatively regulates Akt activation. MATERIALS AND METHODS: The expression of phosphorylated Akt (p-Akt), total Akt and PTEN was analyzed by Western blotting in 45 renal cell carcinoma (RCC) patients. The Bad and phosphorylated Bad (p-Bad) statuses were analyzed in 20 RCC patients. A phosphatidylinositol ether analog was used as an Akt inhibitor to treat four RCC cell lines, namely Caki-1, KU19-20, SW839 and Caki-2. RESULTS: The PTEN expression in RCC was observed to decrease and p-Akt expression to increase significantly in comparison with that in the corresponding normal kidney tissue. The PTEN expression inversely correlated with the p-Akt expression. These alterations were specific for clear cell type RCC, but not for papillary or chromophobe type RCC. Alterations in Bad phosphorylation were also specifically observed in clear cell type. The Akt inhibitor induced apoptosis in KU19-20 and Caki-2 cells with a high Akt activity. CONCLUSIONS: A decreased expression of PTEN may be an underlying mechanism for Akt activation. An Akt inhibitor may be a therapeutic option for a subset of RCC with an elevated Akt activity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  IEP 2292677 RGD 
renal cell carcinoma  ISOBAD (Homo sapiens)2292677; 2292677 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bad  (BCL2-associated agonist of cell death)

Genes (Mus musculus)
Bad  (BCL2-associated agonist of cell death)

Genes (Homo sapiens)
BAD  (BCL2 associated agonist of cell death)


Additional Information