Nuclear mRNA retention and aberrant doppel protein expression in human astrocytic tumor cells.
Nuclear mRNA retention and aberrant doppel protein expression in human astrocytic tumor cells.
复制标题
人星形胶质细胞肿瘤细胞中核 mRNA 保留和异常双蛋白表达。
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
L. Ferretti
中科院分区：
文献类型：
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作者：
S. Comincini;L. Chiarelli;P. Zelini;I. Del Vecchio;A. Azzalin;A. Arias;V. Ferrara;Paola Rognoni;Antonella Dipoto;R. Nano;G. Valentini;L. Ferretti
Doppel (Dpl) is a paralogue of the mammalian Prion (PrP) protein. It is abundant in testis and, unlike PrP, it is expressed at low levels in the adult central nervous system (CNS). Besides, Dpl overexpression correlates with some prion-disease pathological features, such as ataxia and death of cerebellar neurons. Recently, ectopic expression of doppel was found in two different tumor types, specifically in glial and haematological cancers. In this study the doppel gene (PRND) mRNA and protein expression in PRT-HU2 and IPDDC-A2 astrocytoma-derived cell lines was investigated. Northern blot analysis revealed two equally abundant PRND mRNA isoforms, while real-time PCR, on nuclear and cytoplasmic RNA fractions, and cRNA in situ hybridization, on astrocytoma cells and bioptical specimens, showed a nuclear retention of PRND transcripts. Western blot analysis showed that the amount of protein expressed is low compared to the level of mRNA. Moreover deglycosylation studies indicated that Dpl undergoes unusual glycosylation processes. Immunohistochemistry experiments demonstrated that Dpl was mainly localised in the cytoplasm of the astrocytic tumor cells, and that it failed to be GPI-anchored to the cell membrane. This unusual cellular localization was also confirmed through EGFP-Dpl expression in astrocytomas; on the contrary, HeLa cells exhibited the expected Dpl membrane localization. Our findings suggest an aberrant doppel gene expression pattern, characterized by a substantial nuclear retention of the transcript, an altered post-translational modification of the protein and an unusual cytoplasmic localization.
影响因子：
11.2
作者：
B. Rasheed;R. McLendon;J. Herndon;H. Friedman;A. Friedman;D. Bigner;S. Bigner
通讯作者：
B. Rasheed;R. McLendon;J. Herndon;H. Friedman;A. Friedman;D. Bigner;S. Bigner