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Akt signalling parameters are different in oncocytomas compared to renal cell carcinoma
B Amend1, J Hennenlotter, M Scharpf
1Department of Urology, Eberhard Karls University Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany.
Purpose:
Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours.
Methods:
By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed.
Results:
Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9 ± 13.0 versus 75.5 ± 8.0 versus 123.7 ± 8.8; p < 0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7 ± 1.2 versus 40.8 ± 9.5 versus 143.6 ± 12.2; p < 0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3 ± 15.7 vs. 144.0 ± 26.6; p < 0.05).
Conclusion:
All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.
Insights
Renal oncocytomas show significantly lower levels of PTEN, p-Akt, and p27(Kip1) compared to clear cell renal cell carcinoma (ccRCC). These findings offer insights into the molecular mechanisms of renal tumor dedifferentiation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Renal oncocytomas are benign tumors with poorly understood molecular mechanisms.
- The PKB/Akt pathway is implicated in malignant tumor progression, but its role in oncocytomas is unclear.
- Data on Akt signaling parameters in oncocytomas are scarce.
Purpose of the Study:
- To investigate alterations in PTEN, phosphorylated Akt (p-Akt), and p27(Kip1) in renal oncocytomas.
- To compare these parameters between oncocytomas, clear cell renal cell carcinoma (ccRCC), and benign renal tissue.
- To enhance understanding of renal tumor dedifferentiation and the PKB/Akt signaling axis.
Main Methods:
- Tissue microarray analysis of 15 oncocytomas, 18 ccRCCs, and corresponding benign tissues.
- Immunohistochemistry was used to determine the expression levels of PTEN, p-Akt, and p27(Kip1).
- Statistical analyses included One-way ANOVA with Tukey-Kramer post hoc tests and linear regression for parameter interactions.
Main Results:
- PTEN and p27(Kip1) expression was significantly lower in oncocytomas compared to both benign tissue and ccRCC (p < 0.001).
- p-Akt expression was significantly lower in oncocytomas compared to ccRCC (p < 0.05).
- All three investigated proteins showed significantly different expression levels across the groups.
Conclusions:
- PTEN and p27(Kip1) expression levels are markedly reduced in oncocytomas relative to ccRCC.
- The observed low expression of PTEN and p27(Kip1) in oncocytomas may be associated with benign tumor characteristics.
- These findings contribute to understanding the PKB/Akt signaling pathway in renal tumors and tumor dedifferentiation.
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