Abstract
Ras genes, a class of nucleotide-binding proteins that regulate normal and transformed
cell growth, have been scarcely investigated in human brain tumours. We evaluated
the mutational, mRNA and protein expression profile of the ras genes in 21 glioblastomas multiforme (grade IV), four fibrillary astrocytoma (grade
II), four anaplastic astrocytoma (grade III) and 15 normal specimens. K-, H- and N-ras transcript levels were determined by real-time RT-PCR and mutational status by PCR-restriction
fragment length polymorphism (RFLP) and direct sequencing. p21 protein was evaluated
by Western blot analysis. Two K-ras mutations were found in codons 16 and 26 in one pathological and one normal sample,
respectively. Glioblastoma multiforme cases exhibited significantly lower K- and H-ras mRNA levels compared to controls (P < 10–4). K- and H-ras mRNA down-regulation was not associated with patient outcome or survival. K-ras was positively correlated with H-ras in glioblastomas (P = 0.005), but not in normal specimens. p21 protein was absent in all samples. Our findings
provide evidence of K- and H-ras involvement in brain malignant transformation through transcriptional down-regulation,
while N-ras seems to contribute less to brain carcinogenesis.
Keywords
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Article info
Publication history
Published online: January 29, 2009
Accepted:
December 19,
2008
Received in revised form:
December 17,
2008
Received:
September 25,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
