PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas--implications for Akt activation.
Activation of the PKB/Akt pathway is supposed to substantially contribute to the pathogenesis and progression of malignant disease. The present study aimed at determining the occurrence of an impaired PTEN and p27Kip1 expression alone or in combination in a renal cell carcinoma to further clarify the role of Akt-pathway-associated proteins for the development and/or progression of this malignant disease. By using tissue microarray analysis, tissue samples from renal cell cancers and the corresponding benign tissue samples were investigated for expression of the PTEN, pAkt and p27Kip1 protein by immunohistochemistry. Additionally, a Western blot and RT-PCR analysis was performed to verify the results obtained from the immunohistochemical approach and to further clarify the mechanisms underlying the regulation of both proteins in renal cell cancer. Western blot analysis revealed an overexpression of PTEN and p27Kip1 in renal cell cancer samples and a significantly elevated expression of both proteins when compared with the corresponding benign tissue (p<0.0001 and p<0.0005). The latter finding was confirmed by real-time RT-PCR (p<0.05 and p<0.01) and immunohistochemistry (p<0.001 and p<0.0001). PTEN and p27Kip1 expression were positively correlated with each other both in the tumour and benign tissue (p<0.001 and p<0.0001). We concluded that a strong expression of PTEN in renal cell cancer did not block the PI3K-mediated phosphorylation of Akt in the tumour specimens analysed. Furthermore, Akt activation may not result in a decreased p27Kip1, the latter being retained and overexpressed in the majority of renal cell cancers when compared with the corresponding benign renal parenchyma.
Hennenlotter
Joerg
J
Department of Urology, Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany.
Ohneseit
Petra A
PA
Simon
Perikles
P
Merseburger
Axel S
AS
Serth
Juergen
J
Kuehs
Ursula
U
Kramer
Mario
M
Hartmann
Joerg T
JT
Stenzl
Arnulf
A
Kuczyk
Markus A
MA
D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000201:enzymology / Q000378:metabolism*; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human