Poly (ADP-ribose) Polymerase Promoter Hypermethylation Predispose Females to Breast Cancer

H. Sabit, Shaimaa Nazir, Shaimma Abdel-Ghany, Osama A. M. Said, Eman Wagih, Omnia M. Badawy, Ashraf Alzayyat, A. Alqosaibi, E. Çevik, H. Tombuloglu, M. El-Zawahri
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引用次数: 1

Abstract

Being the most common cause of female deaths worldwide, breast cancer (BC) is intensively studied over the last two decades. In the present investigation, we evaluated the promoter methylation of three cancer-related genes; PARP-1, p21, and Rb in 10 bi-matched BC samples (ductal carcinoma and lobular carcinoma) included the core tumor and the adjacent normal tissue. H&E-stained histopathological sectioning revealed grade 2 and grade 3 tumor cells. Methylation-specific PCR (MSP) was performed using methylated (M) and unmethylated (U) primers for the three genes understudy. Histone acetyltransferase was measured in tumor and healthy tissues. A variation in the methylation state of the promoter region of the three genes were observed in core tumor and healthy tissue. PARP and Rb were hypermethylated in tumor tissues while p21 was partially methylated. HAT activities were positively correlated with the methylation pattern observed in healthy tissues, as HAT was highly expressed in healthy vs. tumor tissues. The obtained data might indicate that patients might be at risk of BC recurrence after being subjected to mastectomy. These data could be employed as a core in epigenetic-based data mining to establish a model for predicting the breast cancer-predisposed patients. However, further investigations are needed to fulfill this goal.
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聚(adp -核糖)聚合酶启动子高甲基化使女性易患乳腺癌
作为全世界女性死亡的最常见原因,乳腺癌(BC)在过去二十年中得到了深入研究。在本研究中,我们评估了三个癌症相关基因的启动子甲基化;10例双配对BC样本(导管癌和小叶癌)的PARP-1、p21和Rb包括核心肿瘤和邻近正常组织。h&e染色组织病理切片显示2级和3级肿瘤细胞。使用甲基化(M)和未甲基化(U)引物对这三个基因进行甲基化特异性PCR (MSP)。在肿瘤组织和健康组织中测定组蛋白乙酰转移酶。在核心肿瘤和健康组织中观察到三个基因的启动子区域甲基化状态的变化。PARP和Rb在肿瘤组织中高度甲基化,而p21在肿瘤组织中部分甲基化。HAT活性与健康组织中观察到的甲基化模式呈正相关,因为HAT在健康组织和肿瘤组织中高度表达。所获得的数据可能表明患者在接受乳房切除术后可能有BC复发的风险。这些数据可以作为基于表观遗传学的数据挖掘的核心,建立预测乳腺癌易感患者的模型。然而,要实现这一目标,还需要进一步的研究。
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