[Alzheimer's disease and fragile X syndrome: the Wnt/ß-catenin pathway as a common biological mechanism]. / Enfermedad de Alzheimer y síndrome X frágil: la vía Wnt-ß-catenina como mecanismo biológico común.

INTRODUCTION: Various disorders affecting the canonical Wnt/ß-catenin signalling pathway have been related to the activation or inactivation of oncogenes and tumour suppressor genes that give rise to a number of well-defined neoplasias, as well as several genes involved in a growing group of complaints, including Alzheimer's disease (AD) and fragile X syndrome (FXS). AIM: To examine the Wnt/ß-catenin signalling pathway as a possible common biological mechanism involved in the origin and development of neurodegenerative conditions and its relationship with cancer. DEVELOPMENT: We review the most recent biomedical literature dealing with the Wnt/ß-catenin signalling pathway and its participation in the genesis of complaints such as AD and FXS. An analysis is also conducted to determine the role that this metabolic pathway might play in explaining the lowered risk of developing cancer displayed by these patients. CONCLUSIONS: The evidence found suggests that the Wnt/ß-catenin pathway could be regulating a set of genes linked with the control of the cell cycle and apoptosis. This would give rise to a metabolic state in which, in conditions such as AD and FXS, the cells would be more likely to undergo apoptosis than initiate mitosis, which would in turn account for the reduced risk of developing cancer.

[WNT-ß-catenin signaling pathway and its relationship with cancer]. / La vía de señalización Wnt-ß-catenina y su relación con cáncer.

The Wnt-ß-catenin signalling pathway plays a crucial role in the regulation, differentiation, proliferation and cellular death processes; consequently, alterations in this pathway are involved in numerous abnormalities of development, growth and homeostasis in animal organisms. Wnt proteins include a numerous family of secretion glycoproteins which join to Frizzled receptors and Low Density Lipoprotein Receptor-related Protein, in order to stabilize the critical ß-catenin protein, and to initiate an intricate signaling cascade, which is related to multiple nucleocytoplasmatic processes. Alterations in the canonical Wnt-ß-catenin signaling pathway have been associated with variations in a number of proteins participating in this route, or with activation / inactivation of oncogenes and tumor suppressor genes, which explain different processes of tumorigenesis, in addition to a number of malformations and human diseases. This review describes the relations between the Wnt-ß-catenin signaling pathway with different neoplasic processes, as well as its application in the diagnosis and prognosis of cancer.

Gene expression profiling identifies WNT7A as a possible candidate gene for decreased cancer risk in fragile X syndrome patients.

BACKGROUND AND AIMS: Although sporadic cases of cancer in patients with fragile X syndrome (FXS) have been reported, extensive studies carried out in Denmark and Finland concluded that cancer incidence in these patients is lower than in the general population. On the other hand, the FMR1 protein, which is involved in the translation process, is absent in FXS patients. Hence, it is reasonable to assume that these patients exhibit an abnormal expression of some proteins involved in regulating tumor suppressor genes and/or oncogenes, thus explaining its decreased cancer frequency. We undertook this study to analyze the expression of oncogenes and tumor suppressor genes in fragile X syndrome patients. METHODS: Molecular analysis of the FMR1 gene was achieved in 10 male patients and controls. Total RNA from peripheral blood was used to evaluate expression of oncogenes and tumor suppressor genes included in a 10,000 gene microarray library. Quantitative real-time PCR was utilized to confirm genes with differential expression. RESULTS: Among 27 genes showing increased expression in FXS patients, only eight genes exhibited upregulation in at least 50% of them. Among these, ARMCX2 and PPP2R5C genes are tumor suppressor related. Likewise, 23/65 genes showed decreased expression in >50% of patients. Among them, WNT7A gene is a ligand of the beta-catenin pathway, which is widely related to oncogenic processes. Decreased expression of WNT7A was confirmed by quantitative RT-PCR. Expression of c-Myc, c-Jun, cyclin-D and PPARdelta genes, as target of the beta-catenin pathway, was moderately reduced in FXS patients. CONCLUSIONS: Results suggest that this diminished expression of the WNT7A gene may be related to a supposed protection of FXS patients to develop cancer.