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001-es BibID:BIBFORM042489
Első szerző:Petrás Miklós (orvos)
Cím:Significance of Epidermal Growth Factor Receptor in the Radiation Resistance of Glioblastoma Tumors / Miklós Petrás, Tamás Lajtos, Éva Pintye, Burt G. Feuerstein, János Szöllősi, György Vereb
Megjegyzések:In the United States, a dramatically increased incidence and mortality of brain tumors have been observed over the past decades. Of the ~44 thousand new cases of primary malignant and benign brain tumors diagnosed per year, highgrade astrocytomas or multiform glioblastomas show particularly bad prognosis in spite of therapeutic developments. Current management of multiform glioblastoma includes the most extensive surgical resection possible, followed by adjuvant radio- and chemotherapy. However, treatment is frequently hampered by decreased radiosensitivity of the tumor. Recent studies revealed that subpopulations of glioblastoma cells show amplified checkpoint activation of the cell cycle upon ionizing radiation, which induces overactivation of DNA repair processes and leads to maintained proliferation rate as well as clinically observed radioresistance and recurrence of the tumor over time. In addition, overexpression of some transmembrane receptors has also been implicated in radioresistance. However, the role of the overexpressed proteins can only be interpreted reliably if their multi-faceted molecular interactions are properly characterized. Thus, based on recent evidence for the functional crosstalk between certain cell adhesion molecules andreceptor tyrosine kinases, we have examined the molecular interactions of the receptor tyrosine kinase EGFR and the cell adhesion molecule 1-integrin using flow cytometric and microscopic fluorescence resosnance energy transfer (FRET)measurements on two cellular model systems showing similar expression patterns to low and high grade astrocytomas. On the one hand, U251 glioblastoma clones established by introducing varying amounts of extra chromosome 7 into the cells, and on the other hand stable, high and low EGFR expressing transfenctant U251 NCI sublines were investigated. The results revealed that increased EGFR and 1-integrin expression levels correlate with stronger EGFR ? 1-integrin heteroassociation, while concurrently the EGFR homoassociation is decreased, suggesting that 1-integrins may dynamically modulate the homoassociation state of EGFR receptors. This functional relationship may play an important role in decreasing radiosensitivity and tumor progression, especially since the EGFR ? 1-integrin molecular interaction appears to promote radioresistance via the Akt pathway.
Tárgyszavak:Orvostudományok Elméleti orvostudományok könyvfejezet
Megjelenés:Radiation Damage In Biomolecular Systems : Proceedings of the 5th International Conference (RADAM 2008) / ed. by Károly Tőkési, Béla Sulik. - p. 204-217. -
További szerzők:Lajtos Tamás Pintye Éva (1955-) (fizikus) Feuerstein, Burt G. Szöllősi János (1953-) (biofizikus) Vereb György (1965-) (biofizikus, orvos)
Internet cím:DOI
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