RESUMO
Aberrant expression of vascular endothelial growth factor (VEGF) is associated with human prostate cancer (PCa) metastasis and poor clinical outcome. We found that both phosphorylation of cyclic AMP-responsive element-binding protein (CREB) and VEGF levels were significantly elevated in patient bone metastatic PCa specimens. A PCa ARCaP progression model demonstrating epithelial-to-mesenchymal transition exhibited increased CREB phosphorylation and VEGF expression as ARCaP cells became progressively more mesenchymal and bone-metastatic. Activation of CREB induced, whereas inhibition of CREB blocked, VEGF expression in ARCaP cells. CREB may regulate VEGF transcription via a hypoxia-inducible factor-dependent mechanism in normoxic conditions. Activation of CREB signaling is involved in the coordinated regulation of VEGF and may pre-dispose to PCa bone metastasis.
Assuntos
Neoplasias Ósseas/secundário , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Regiões Promotoras Genéticas , Neoplasias da Próstata/química , Neoplasias da Próstata/metabolismo , Transcrição Gênica , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Two genes, i.e. survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) have been mapped to the SMA region of chromosome 5q13. Both genes are frequently deleted or truncated in SMA patients. We have studied 26 patients with SMA types I-III, 29 first relatives, and 14 subjects with mild adult-onset type IV. DNA deletion genotypes were determined by PCR techniques amplifying exons 7 and 8 of SMN, and exon 5 of NAIP gene which distinguish SMN and NAIP telomeric copy from a non-pathogenic gene homologue as a centromeric copy. Results revealed the homozygous deletions of exon 7 and 8 of the SMN gene and exon 5 of the NAIP gene in 3/3 infants with SMA I and in 1/20 with SMA type II. Exons 7 and 8 of the SMN gene were homozygously deleted in 10/20 and only exon 7 in 6/20 children with SMA type II. The overall percentage of deletion cases observed was 77% in children with SMA types I-III. Adult patients with type IV SMA showed no homozygous deletion of exons 7, 8 and 5 of the SMN and NAIP genes. Also, all relatives had both a telomeric and centromeric SMN and NAIP copy. Deletion analysis of SMN and NAIP genes are a significant diagnostic tool, because there are clinical entities resembling SMA which most likely have another pathogenetic background.
Assuntos
Atrofia Muscular Espinal/genética , Proteínas do Tecido Nervoso/genética , Atrofias Musculares Espinais da Infância/genética , Adulto , Criança , Pré-Escolar , Croácia , Análise Mutacional de DNA , Éxons , Deleção de Genes , Humanos , LactenteRESUMO
A case of neuro-cutaneous melanoma, in the course of which a bifocal melanoma of the cerebral hemisphere had developed, was used as a natural model for the study of the relation between tumorous and non-tumorous elements. The need is pointed out for the definition of such a cutaneous-meningeal syndrome before the development of a neoplasm. As tumours develop from the cells defining leptomeningeal melanosis, the possibility of a neuroradiological diagnosis of this process is accentuated, primarily by a minute examination of the sites characteristic of the disease. A premorbid detection of all such cases is imperative in order to introduce an early anti-tumour treatment.