RESUMO
Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ciclo Celular/genética , Dineínas/genética , Glioblastoma/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ciclo Celular/análise , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Dineínas/análise , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico , Glioblastoma/patologia , Fatores de Troca do Nucleotídeo Guanina/análise , Humanos , Imuno-Histoquímica , Estadiamento de Neoplasias , Nucleofosmina , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Troca de Nucleotídeo Guanina RhoAssuntos
Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica/métodos , Glioma/genética , Análise de Sequência com Séries de Oligonucleotídeos , Apoptose/genética , Neoplasias Encefálicas/patologia , Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos/genética , Genes Supressores de Tumor , Humanos , Invasividade Neoplásica/genética , Transdução de Sinais/genéticaRESUMO
Human CC ligand 3-like protein 1 (CCL3L1), a member of the CC chemokine family, that induces MCP1 and RANTES, exhibits a variety of proinflammatory activities including chemotaxis, and functional and proliferative activation of leukocytes, lymphocytes and macrophages. Its signal is transmitted through transmembrane receptors, CC chemokine receptors, CCR1, CCR3 and CCR5. To examine gene expression of chemokine, CCL3L1, and its receptors, CCR1, CCR3 and CCR5, we analyzed tumor tissues from 21 patients with several types of primary gliomas. CCL3L1, CCR3 and CCR5 gene exhibited over-expression in 70% (7/10), 60% (6/10), and 60% (6/10) of glioblastoma, in comparison with lower frequencies seen in lower-grade gliomas. Transfection of CCL3L1-expression vector to glioblastoma cell line enhanced proliferation of the tumor cells. These data suggest that increased expression of the CCL3L1, CCR3 and CCR5 chemokine-receptors system is involved in brain tumorigenesis, especially in the progression of glioblastoma.
Assuntos
Neoplasias Encefálicas/metabolismo , Quimiocinas CC/biossíntese , Glioblastoma/metabolismo , Receptores CCR5/biossíntese , Receptores de Quimiocinas/biossíntese , Proliferação de Células , Expressão Gênica , Humanos , RNA Mensageiro/análise , Receptores CCR3 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Regulação para CimaRESUMO
Familial ependymal tumors are a very rare disease, the pathogenesis of which is unknown. Previous studies indicate an involvement of tumor suppressor genes localized within chromosomal region 22q, whereas details are still unclear. Here we report a non-neurofibromatosis type-2 (non-NF2) Japanese family in which two of the four members are affected with cervical spinal cord ependymoma, and one of the four is affected with schwannoma. Loss of heterozygosity (LOH) studies were carried out searching for common allelic loss at chromosomal region 22q11.2-qtel in two of the affected patients. Our findings support a prediction for existence of a tumor suppressor gene on chromosome 22 especially related to the tumorigenesis of familial ependymal tumors.
