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- W2037806586 abstract "Reduced expression of the secreted growth factor progranulin (GRN) in brain due to haploinsufficiency or miRNA-mediated downregulation was demonstrated to cause ubiquitin- and TDP43-positive frontotemporal dementia (FTLD-U). Consequently, pharmacological upregulation of PGRN expression has been proposed as a potential strategy for treatment or prevention of FTLD-U. However, GRN has been found to be overexpressed in a variety of cancer cells and was shown to function as an autocrine stimulant of proliferation and invasive behavior. This association of GRN with multiple cancers indicates that upregulation of GRN expression in FTLD-U patients might pose potential risks that need to be carefully evaluated. To investigate whether increased expression and signaling of GRN might contribute to the development or progression of human brain tumors. GRN expression in human brain tumors, normal brain tissue and human glioblastoma cell lines was assessed by quantitative real-time PCR, immunohistochemistry and Western blotting. By immunohistochemistry, we have confirmed that in normal brain GRN is predominantly expressed in neurons and microglia cells, while expression in white matter was only weak or completely absent. Strikingly, in a tissue microarray consisting of 38 glioblastomas WHO grade IV, 13 anaplastic astrocytomas WHO grade III and 7 astrocytomas WHO grade II, GRN expression was detected in all tumors with the exception of one glioblastoma with sarcomatous component. GRN protein was clearly present in the cytoplasm of tumor cells and not in stroma cells. Furthermore, quantitative real-time PCR analysis demonstrated 5-20 fold overexpression of GRN in some high-grade astrocytomas and oligodendrogliomas as compared to normal brain samples. In a panel of human glioblastoma cell lines robust but variable GRN expression was demonstrated in 8/8 cell lines. The near ubiquitous expression of GRN in human gliomas as compared to the highly restricted expression pattern in normal brain tissue suggests that GRN signaling could have a role in development of human gliomas, and that disproportionate upregulation of GRN expression might increase the susceptibility of FTLD-U patients to brain tumors. Studies are ongoing to clarify the functional relevance of GRN expression in human gliomas." @default.
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- W2037806586 date "2009-07-01" @default.
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- W2037806586 title "P4-244: Progranulin (GRN), a protein mutated in frontotemporal dementia with ubiquitin-positive inclusions (FTLD-U), is abundantly expressed in human gliomas" @default.
- W2037806586 doi "https://doi.org/10.1016/j.jalz.2009.04.710" @default.
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