Rodríguez-Jiménez Francisco-Javier, Caldés Trinidad, Iniesta Pilar, Vidart Jose Antonio, Garcia-Asenjo José López, Benito Manuel
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Oncol Rep. 2007 Jun;17(6):1301-7.
Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular glycoprotein involved in crucial processes that occur during cancer. This study explored the occurrence of deregulated expression of SPARC in endometrial carcinomas, since it has been associated with the progression of other tumor types. We analyzed the expression of SPARC in endometrial carcinomas by TaqMan, Western blotting and immunohistochemistry. The CpG island methylation status of SPARC was evaluated by bisulfite sequencing method. A significant down-regulation of SPARC mRNA expression (p<0.001) was observed in endometrial tumor tissues, regardless of their microsatellite instability status (MSI). The down-regulation can be accounted for by aberrant hypermethylation of its CpG-rich region, since we demonstrate that SPARC is a frequent target of this epigenetic event in this pathology. Although, differential expression of SPARC is already known in other cancer types, we report that down-regulation of the SPARC gene in endometrial tumors, formed by at least 80% of epithelial tumor cells, contrasts with a frequent overexpression of SPARC protein, with strong immunoreactivity in stromal cells. These results indicate a cell type specific expression of SPARC in endometrial carcinomas. Accumulation of SPARC protein in most tumors compared to normal tissues (p<0.025), suggests an important role in the carcinogenesis of endometrial tumors. SPARC overexpression can be a useful molecular tool that may contribute to the diagnosis of this disease.
富含半胱氨酸的酸性分泌蛋白（SPARC）是一种分泌型基质细胞糖蛋白，参与癌症发生过程中的关键进程。本研究探讨了SPARC在子宫内膜癌中表达失调的情况，因为它与其他肿瘤类型的进展有关。我们通过TaqMan、蛋白质免疫印迹法和免疫组织化学分析了SPARC在子宫内膜癌中的表达。采用亚硫酸氢盐测序法评估SPARC的CpG岛甲基化状态。在子宫内膜肿瘤组织中观察到SPARC mRNA表达显著下调（p<0.001），无论其微卫星不稳定性状态（MSI）如何。这种下调可归因于其富含CpG区域的异常高甲基化，因为我们证明在这种病理情况下SPARC是这种表观遗传事件的常见靶点。虽然SPARC在其他癌症类型中的差异表达已经为人所知，但我们报告，在由至少80%的上皮肿瘤细胞形成的子宫内膜肿瘤中，SPARC基因下调，而SPARC蛋白却频繁过度表达，在基质细胞中具有强免疫反应性。这些结果表明SPARC在子宫内膜癌中具有细胞类型特异性表达。与正常组织相比，大多数肿瘤中SPARC蛋白积累（p<0.025），提示其在子宫内膜肿瘤发生中起重要作用。SPARC过度表达可能是一种有用的分子工具，有助于这种疾病的诊断。
