Differential expression of the prion-like protein doppel gene (PRND) in astrocytomas: A new molecular marker potentially involved in tumor progression

Sergio Comincini, Angelica Facoetti, Igor Del Vecchio, Katell Peoc'h, Jean Louis Laplanche, Lorenzo Magrassi, Mauro Ceroni, Luca Ferretti, Rosanna Nano

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Abstract

The expression of the prion (PRNP) and prion like-doppel (PRND) genes and the presence of the proteins prion (PrP) and doppel (Dpl) were investigated in human gliomas. The PRNP and PRND expression profiles were evaluated by real-time reverse transcription-quantitative PCR in low- and high-grade astrocytomas, in glioblastoma-derived cell lines and in non-glial tumor specimens. The presence of PrP and Dpl proteins and their cellular localization were evaluated by Western blot and immunohistochemistry. High levels of PRNP expression were found in all tumoral samples studied. Unlike the non-tumoral controls, PRND was aberrantly expressed in glioblastoma multiforme and in two glioblastoma multiforme-derived cell lines, even in the absence of the PRND gene amplification. PRND expression was directly related to malignancy of the tumor: highest in glioblastoma multiforme, lower in anaplastic astrocytoma and even lower in the low-grade astrocytoma samples. High levels of PRND were also found in non-glial malignant tumor samples, such as gastric adenocarcinoma and anaplastic meningioma. Western blot analysis confirmed the PrP and Dpl expression, displaying variability in the electrophoretic patterns. Immunohistochemical analysis revealed a diffuse cytoplasmatic Dpl distribution in different astrocytic neoplastic cells, in infiltrating lymphocytes and in blood vessel endothelial cells. Of note, Dpl reactivity was different from that of the PrP, since PrP showed typical Golgi and membrane localised staining. Our findings suggest that the PRND gene might be a useful molecular marker in astrocytoma progression and in tumor grade definition. Understanding of the mechanisms of PRND increased expression might provide insight into the regulatory pathways of glioma development.

Original languageEnglish
Pages (from-to)1507-1517
Number of pages11
JournalAnticancer Research
Volume24
Issue number3 A
Publication statusPublished - May 2004

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Keywords

  • Doppel gene expression
  • Glioblastoma multiforme
  • Prion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Comincini, S., Facoetti, A., Del Vecchio, I., Peoc'h, K., Laplanche, J. L., Magrassi, L., Ceroni, M., Ferretti, L., & Nano, R. (2004). Differential expression of the prion-like protein doppel gene (PRND) in astrocytomas: A new molecular marker potentially involved in tumor progression. Anticancer Research, 24(3 A), 1507-1517.