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  • Hede, Sanna-MariaKarolinska Institutet (author)

GFAP promoter driven transgenic expression of PDGFB in the mouse brain leads to glioblastoma in a Trp53 null background

  • Article/chapterEnglish2009

Publisher, publication year, extent ...

  • Wiley,2009
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-124243
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-124243URI
  • https://doi.org/10.1002/glia.20837DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:119124322URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Glioblastomas are the most common and malignant astrocytic brain tumors in human adults. The tumor suppressor gene TP53 is commonly mutated and/or lost in astrocytic brain tumors and the TP53 alterations are often found in combination with excessive growth factor signaling via PDGF/PDGFRalpha. Here, we have generated transgenic mice over-expressing human PDGFB in brain, under control of the human GFAP promoter. These mice showed no phenotype, but on a Trp53 null background a majority of them developed brain tumors. This occurred at 2-6 months of age and tumors displayed human glioblastoma-like features with integrated development of Pdgfralpha+ tumor cells and Pdgfrbeta+/Nestin+ vasculature. The transgene was expressed in subependymal astrocytic cells, in glia limitans, and in astrocytes throughout the brain substance, and subsequently, microscopic tumor lesions were initiated equally in all these areas. With tumor size, there was an increase in Nestin positivity and variability in lineage markers. These results indicate an unexpected plasticity of all astrocytic cells in the adult brain, not only of SVZ cells. The results also indicate a contribution of widely distributed Pdgfralpha+ precursor cells in the tumorigenic process.

Subject headings and genre

  • NEURAL STEM-CELLS
  • GROWTH-FACTOR-B
  • ALPHA-RECEPTOR EXPRESSION
  • AUTOCRINE STIMULATION
  • MALIGNANT GLIOMAS
  • GLIAL TUMORS
  • P53
  • MICE
  • CNS
  • PROGENITORS;
  • MEDICINE
  • MEDICIN

Added entries (persons, corporate bodies, meetings, titles ...)

  • Hansson, IngaUppsala universitet,Institutionen för genetik och patologi (author)
  • Afink, Gijs B (author)
  • Eriksson, AnnaKarolinska Institutet (author)
  • Nazarenko, Inga (author)
  • Andrae, JohannaKarolinska Institutet (author)
  • Genove, GuillemKarolinska Institutet (author)
  • Westermark, BengtUppsala universitet,Institutionen för genetik och patologi(Swepub:uu)bengtwm (author)
  • Nistér, MonicaKarolinska Institutet (author)
  • Karolinska InstitutetInstitutionen för genetik och patologi (creator_code:org_t)

Related titles

  • In:Glia: Wiley57:11, s. 1143-11530894-14911098-1136

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