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Different glioblastoma multiforme subgroups exist with regards to EGFR and PDGFRα activation
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-90475OAI: oai:DiVA.org:uu-90475DiVA: diva2:162840
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved
In thesis
1. A Short Thesis about Growth Factors in Gliomas
Open this publication in new window or tab >>A Short Thesis about Growth Factors in Gliomas
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in humans. Its aggressive and infiltrative growth into the brain, and, at best, only partial sensitivity to radiotherapy and chemotherapy, renders it extremely difficult to treat and survival remains dismal.

Growth factors, such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF), and their corresponding receptors are seen in glioma tissue, suggesting the presence of autocrine stimulatory loops. PDGFB and a mutated EGF receptor were also identified as cellular homologues of two oncoviruses, thereby indicating a role in tumorigenesis. This thesis presents a brain tumor model in mice, developed using a PDGFB coding retrovirus to induce overexpression of PDGF-B in neonatal mouse brain. Immature tumors, with histological characteristics of primary brain tumors developed at relatively high frequencies. Mice injected with a non-coding retrovirus did not develop tumors, indicating the crucial role of PDGF stimulation in this system. Tumor cells were also shown to continue to depend on PDGF stimulation when cultured in vitro.

In human glioblastomas, growth factor receptor signaling is present in conjunction with defects in cell cycle arrest pathways. When the PDGFB-virus model was used with p53 or Ink4a-Arf deficient mice, tumors arose with shorter latency and higher frequency. Loss of p53 or Ink4a-Arf seemed to facilitate signaling through the PI3K/Akt pathway. Thus, a functional role for the co-existence of p53 loss of function and PDGF signaling in a subset of gliomas is presented.

Human GBM samples were collected and analyzed with respect to expression and activation of the EGFR and PDGFRα. Most tumors expressed the both receptors at moderate to high levels, but high activation of either receptor seemed mutually exclusive.

Place, publisher, year, edition, pages
Uppsala University Library, 2003. 67 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1250
Pathology, glioma, mouse model, PDGF, EGFR, activation, Patologi
National Category
Cell and Molecular Biology
Research subject
urn:nbn:se:uu:diva-3445 (URN)91-554-5602-2 (ISBN)
Public defence
2003-05-19, Rudbecksalen, Rudbecklaboratoriet, Uppsala, 09:15
Available from: 2003-04-25 Created: 2003-04-25Bibliographically approved

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