Gene Expression Profiling Identifies WNT7A As a Possible Candidate Gene for Decreased Cancer Risk in Fragile X Syndrome Patients
Gene Expression Profiling Identifies WNT7A As a Possible Candidate Gene for Decreased Cancer Risk in Fragile X Syndrome Patients
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DOI：
10.1016/j.arcmed.2010.03.001
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发表时间：
2010-02-01
影响因子：
7.7
通讯作者：
Barros-Nunez, Patricio
中科院分区：
文献类型：
--
作者：
Alejandra Rosales-Reynoso, Monica;Berenice Ochoa-Hernandez, Alejandra;Barros-Nunez, Patricio
背景和目的。虽然有报道称脆性X染色体综合征（FXS）患者中有散发的癌症病例，但在丹麦和芬兰进行的广泛研究得出结论，这些患者的癌症发病率低于一般人群。另一方面，参与翻译过程的FMR1蛋白在FXS患者中缺失。因此，我们有理由认为这些患者表现出一些参与调节肿瘤抑制基因和/或癌基因的蛋白质的异常表达，从而解释了其癌症发生率降低的原因。本研究旨在分析脆性X综合征患者癌基因和抑癌基因的表达情况。在10例男性患者和对照组中进行了FMR1基因的分子分析。来自外周血的总RNA用于评估包含在10,000个基因微阵列文库中的癌基因和肿瘤抑制基因的表达。采用实时荧光定量PCR技术对差异表达基因进行鉴定。在FXS患者中27个表达升高的基因中，只有8个基因表达上调，至少占50%。其中，ARMCX2和PPP2R5C基因与肿瘤抑制基因相关。同样，有23/65个基因在50%的患者中表达降低。其中，WNT7A基因是β -连环蛋白通路的配体，与致癌过程广泛相关。定量RT-PCR证实WNT7A表达降低。作为β -catenin通路靶点的c-Myc、c-fun、cyclin-D和PPAR δ基因的表达在FXS患者中中度降低。结果表明，WNT7A基因表达的减少可能与FXS患者患癌症的保护作用有关。(c) 2010 imss。Elsevier Inc.出版。
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-fun, cyclin-D and PPAR delta 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. (C) 2010 IMSS. Published by Elsevier Inc.