ABSTRACT
In this study we examined by QRT-PCR the mRNA expression of TGF-beta 1, IGF-1, EGF, FGF-2 and YY1 in human brain tumors. Our findings introduce YY1, for the first time, as a novel gene implicated in brain gliomatogenesis and meningioma establishment. We present a positive correlation between the autocrine expression of YY1 and TGF-beta 1, IGF-1 and FGF-2, known to be involved in the progression of gliomas and meningiomas. We suggest that mRNA profiling of the above genes in the early stages of disease development could be useful for prognostic purposes, and these genes can be considered as potential targets for therapeutic approaches against brain tumors.
Subject(s)
Brain Neoplasms/metabolism , Fibroblast Growth Factor 2/genetics , Glioma/metabolism , Insulin-Like Growth Factor I/genetics , Meningioma/metabolism , RNA, Messenger/analysis , Transforming Growth Factor beta1/genetics , YY1 Transcription Factor/genetics , Adult , Aged , Brain Neoplasms/etiology , Female , Glioma/etiology , Humans , Male , Meningioma/etiology , Middle Aged , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
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.
