PTPIP51 and its regulation in tumour cells
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Abstract
To sum up, PTPIP51 is overexpressed in prostate carcinoma compared to benign prostate hyperplasia and in glioblastoma WHO grade IV compared to WHO grade II astrocytoma. In both tumour entities PTPIP51 shows a tissue specific expression profile.For the first time we could link the methylation status of PTPIP51 in prostate carcinoma and benign prostate hyperplasia to the observed altered expression profiles. Here we found a hypomethylation in prostate cancer, which was not seen in benign prostate hyperplasia. This probably explains the higher expression of PTPIP51 in PCa in comparison to BPH on protein level which is reflected on the mRNA level.The interaction of PTPIP51 with 14-3-3beta was identified to lead to a ternary complex with cRAF (Raf1) stimulating the downstream effector of the EGFR/MAPK signaling-pathway. This pathway plays an essential role in cell proliferation and migration, which is especially crucial for the progression of carcinoma. The co-localization of PTPIP51 with 14-3-3beta, Raf-1 and PTP1B was as well identified in prostate carcinoma as in glioblastoma. These findings underline the important role of PTPIP51 in the EGFR/MAPK pathway in cancer. PTP1B is expressed in the investigated tumour samples displaying a similar cellular distribution comparable to that of PTPIP51. As PTP1B regulates the phosphorylation status of PTPIP51, which in turn regulates the interaction of PTPIP51 with 14-3-3beta, we postulate a changed interaction profile of PTPIP51 in tumours.Glioblastoma overexpress EGFR as well as the mutant form EGFRvIII. Therefore, the regulatory potential of PTPIP51 on the downstream part of the EGFR/MAPK pathway was investigated in glioblastoma cells. Interestingly, we were able to demonstrate a direct correlation between the successful inhibition of EGFR by the tyrosine kinase inhibitor Gefitinib treatment led to downregulated expression of PTPIP51 and 14-3-3beta on protein level and a changed interaction profile, emphasizing the important influence of PTPIP51 on EGFR signaling in tumours.In summary, these investigations present an important basis for numerous following studies of PTPIP51 regulation in tumours. Of particular interest is the functional implication of PTPIP51 in neuroepithelial tumours and its clinical relevance as molecular marker in staging or as a target in new therapy strategies.Link to publications or other datasets
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