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首页> 外文期刊>Gene Therapy and Molecular Biology >Transcriptional activation of the ras oncogenes and implications of BRCA1 in the cell cycle regulationthrough p53 checkpoint
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Transcriptional activation of the ras oncogenes and implications of BRCA1 in the cell cycle regulationthrough p53 checkpoint

机译：ras癌基因的转录激活及BRCA1在p53检查点调控细胞周期中的作用

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Aberrant expression of ras genes has been recognized in several human cancers and is associated with the development of the disease. Thus, revealing the mechanisms that regulate the expression of ras genes is critical for understanding their role in the process of tumorigenesis. Transcriptional regulation of the H-ras gene, involves nuclear factors recognizing elements in the promoter region of the gene and hormones; so far, a glucocorticoid response element and a p53 element have been identified. Alternative splicing and specific methylation patterns may regulate the expression of ras genes as well. Altered expression of ras genes has been detected in a variety of human tumours. Differential expression of the ras family genes in breast cancer has shown overexpression of all three members of ras genes. A significant correlation of overexpression of ras genes and stage of the disease was also observed suggesting that aberrant expression of the ras genes may be an initial event in breast cancer oncogenesis. Overexpression of Ras p21 protein has been detected in human endometrial and ovarian tumours, due to elevated p53 protein binding on the p53 element of the c-H-ras gene, suggesting that p53 protein participates in the development of human gynecological neoplasias through aberrant transcriptional regulation of the H-ras proto-oncogene. Investigation of the BRCA1 expression levels in relevance with the expression levels of p53, mdm-2 and p21WAF1/CIP1 genes, implicated in cell cycle progression, revealed combined alterations of these genes in sporadic breast cancer specimens, indicating that loss of function of BRCA1 may arrest the cell cycle through p53 checkpoint.
机译：ras基因的异常表达已在几种人类癌症中得到公认，并与疾病的发展有关。因此，揭示调节ras基因表达的机制对于了解其在肿瘤发生过程中的作用至关重要。 H-ras基因的转录调控涉及识别该基因启动子区域中的元素的核因子和激素。迄今为止，已经鉴定出糖皮质激素反应元件和p53元件。选择性剪接和特异性甲基化模式也可能调节ras基因的表达。在多种人类肿瘤中已检测到ras基因表达的改变。 ras家族基因在乳腺癌中的差异表达表明ras基因的所有三个成员均过表达。还观察到ras基因的过表达与疾病阶段的显着相关性，提示ras基因的异常表达可能是乳腺癌癌发生中的初始事件。由于cH-ras基因的p53元件上p53蛋白的结合增加，已在人的子宫内膜和卵巢肿瘤中检测到Ras p21蛋白的过表达，这表明p53蛋白通过异常的转录调控参与人类妇科肿瘤的发展。 H-ras原癌基因。与细胞周期进程有关的与p53，mdm-2和p21WAF1 / CIP1基因表达水平相关的BRCA1表达水平的研究揭示了散发性乳腺癌标本中这些基因的组合改变，表明BRCA1功能可能丧失通过p53检查点阻止细胞周期。

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