RT info:eu-repo/semantics/article
T1 Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status
A1 Navarro Cerveró, Lara
A1 Gil-Benso, Rosario
A1 Megías Vericat, Javier
A1 Muñoz-Hidalgo, Lisandra
A1 San-Miguel, Teresa
A1 Callaghan, Robert C.
A1 González-Darder, José Manuel
A1 López-Ginés, Concha
A1 Cerdá-Nicolás, Miguel J.
K1 Epidermal growth factor receptor wild type (EGFRwt)
K1 Epidermal growth factor receptor variant III (EGFRvIII)
K1 Glioblastoma (GBM)
K1 Multiplex ligation-dependent probe amplification (MLPA)
K1 Major vault protein (MVP)
K1 Phosphatase and tensin homolog (PTEN)
AB Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression.The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients’ survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) gene dosages. Fluorescent in situ hybridization revealed polysomy of chromosome 7 in 76.1% of the GBMs and EGFR amplification in a 64.6% of the tumors. Genetic status of EGFR, PTEN and MVP copies was determined by multiplex ligation-dependent probe amplification (MLPA) technique. 31% of the tumors showed the EGFR is variant III mutation (EGFRvIII) mutation and 74.3% of them presented amplification of MVP gene. Amplification of EGFR and MVP was found in a 63.7% and 56.6% of the GBM, respectively. An inverse correlation between MVP and PTEN dosage values was observed. Besides, an inverse relationship between the survival of the patients treated with chemotherapy and the levels of MVP copies was determined. In conclusion, our study reveals an important role of MVP, together with EGFRvIII and PTEN, in the progression of GBM and proposes it as a novel and interesting target for new treatment approaches.
SN 1873-7544
YR 2015
FD 2015
LK http://riull.ull.es/xmlui/handle/915/36182
UL http://riull.ull.es/xmlui/handle/915/36182
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 24-nov-2024