Abstract |
Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is an interaction partner of 14-3-3β, which correlates with the grade of malignancy in gliomas. In this study PTPIP51 and its interacting partners 14-3-3β, PTP1B, c-Src, Raf-1 as well as EGFR were investigated in human glioblastoma. Twenty glioblastoma samples were analyzed on transcriptional and translational level by immunohistochemistry, in situ hybridization and RT-PCR. To compare PTPIP51 expression in gliomas of different malignancies, quantitative RT-PCR for grade II astrocytoma and GBM samples was employed. Additionally, we analyzed the correlation between PTPIP51 and 14-3-3β transcription, and checked for in situ interaction between PTPIP51 and 14-3-3β and PTP1B, respectively. PTPIP51 and 14-3-3β mRNA showed a tumour grade dependent upregulation in gliomas. Glioblastoma cells displayed a strong immunoreaction of PTPIP51, which co-localized with 14-3-3β and PTP1B. The duolink proximity ligation assay corroborated a direct in situ interaction of PTPIP51 with both proteins, known to interact with PTPIP51 in vitro. The in vitro interacting partners Raf-1 and c-Src showed a partial co-localization. Besides, immune cells located in capillaries or infiltrating the tumour tissue and endothelial cells of pseudoglomerular vessels revealed a high PTPIP51 expression. The upregulation of PTPIP51 and its connection with the EGFR/MAPK pathway by 14-3-3β via Raf-1 and by PTP1B via c-Src, argue for a functional role of PTPIP51 in the pathogenesis of human glioblastoma.
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Authors | M K Petri, P Koch, A Stenzinger, K Kuchelmeister, U Nestler, A Paradowska, K Steger, A Brobeil, M Viard, M Wimmer |
Journal | Histology and histopathology
(Histol Histopathol)
Vol. 26
Issue 12
Pg. 1531-43
(12 2011)
ISSN: 1699-5848 [Electronic] Spain |
PMID | 21972092
(Publication Type: Journal Article)
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Chemical References |
- 14-3-3 Proteins
- Mitochondrial Proteins
- RNA, Messenger
- YWHAB protein, human
- src-Family Kinases
- Proto-Oncogene Proteins c-raf
- Extracellular Signal-Regulated MAP Kinases
- PTPN1 protein, human
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
- Protein Tyrosine Phosphatases
- RMDN3 protein, human
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Topics |
- 14-3-3 Proteins
(analysis, genetics)
- Adult
- Aged
- Brain Neoplasms
(enzymology, genetics, pathology)
- Extracellular Signal-Regulated MAP Kinases
- Female
- Germany
- Glioblastoma
(enzymology, genetics, pathology)
- Humans
- Immunohistochemistry
- In Situ Hybridization
- MAP Kinase Signaling System
- Male
- Middle Aged
- Mitochondrial Proteins
(analysis, genetics)
- Neoplasm Grading
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
(analysis, genetics)
- Protein Tyrosine Phosphatases
(analysis, genetics)
- Proto-Oncogene Proteins c-raf
(analysis)
- RNA, Messenger
(analysis)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Up-Regulation
- Young Adult
- src-Family Kinases
(analysis)
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