PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas : implications for Akt activation

Autoren

Joerg Hennenlotter
Petra A Ohneseit
Perikles Simon
Axel S Merseburger
Juergen Serth
Ursula Kuehs
Mario Kramer
Joerg T Hartmann
Arnulf Stenzl
Markus A Kuczyk

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000255312000010&DestLinkType=FullRecord&DestApp=WOS_CPL

Externe Identifier

Clarivate Analytics Document Solution ID: 293CI
PubMed Identifier: 18425369

ISSN

1021-335X

Ausgabe der Veröffentlichung

5

Zeitschrift

ONCOLOGY REPORTS

Schlüsselwörter

renal cell cancer
Akt
PTEN
RT-PCR
p27(Kip1)

Paginierung

1141 - 1147

Datum der Veröffentlichung

2008

Status

Published

Titel

PTEN and p27<SUP>Kip1</SUP> are not downregulated in the majority of renal cell carcinomas -: implications for Akt activation

Sub types

Article

Ausgabe der Zeitschrift

19

Data source: Web of Science (Lite)

Abstract

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.

Addresses

Department of Urology, Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany.

Autoren

Joerg Hennenlotter
Petra A Ohneseit
Perikles Simon
Axel S Merseburger
Juergen Serth
Ursula Kuehs
Mario Kramer
Joerg T Hartmann
Arnulf Stenzl
Markus A Kuczyk

eISSN

1791-2431

Externe Identifier

PubMed Identifier: 18425369

Open access

false

ISSN

1021-335X

Ausgabe der Veröffentlichung

5

Zeitschrift

Oncology reports

Schlüsselwörter

Kidney
Humans
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
Immunohistochemistry
Signal Transduction
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Enzyme Activation
Phosphorylation
Cyclin-Dependent Kinase Inhibitor p27
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase

Sprache

eng

Medium

Print

Paginierung

1141 - 1147

Datum der Veröffentlichung

2008

Status

Published

Datum der Datenerfassung

2008

Titel

PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas--implications for Akt activation.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

19

Data source: Europe PubMed Central

Abstract

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.

Autoren

Joerg Hennenlotter
Petra A Ohneseit
Perikles Simon
Axel S Merseburger
Juergen Serth
Ursula Kuehs
Mario Kramer
Joerg T Hartmann
Arnulf Stenzl
Markus A Kuczyk

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/18425369

ISSN

1021-335X

Ausgabe der Veröffentlichung

5

Zeitschrift

Oncol Rep

Schlüsselwörter

Carcinoma, Renal Cell
Cyclin-Dependent Kinase Inhibitor p27
Enzyme Activation
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Kidney
Kidney Neoplasms
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
PTEN Phosphohydrolase
Phosphorylation
Proto-Oncogene Proteins c-akt
Signal Transduction

Sprache

eng

Country

Greece

Paginierung

1141 - 1147

Datum der Veröffentlichung

2008

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2008

Titel

PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas--implications for Akt activation.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

19

Data source: PubMed

PTEN and p27Kip1 are not downregulated in the majority of renal cell carcinomas : implications for Akt activation

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