Decreased Expression of Proapoptotic Genes Caspase-8- and BCL2-Associated Agonist of Cell Death (BAD) in Ovarian Cancer

Nasim Borhani , Mehdi Manoochehri , Soraya Saleh Gargari , Marefat Ghaffari Novin , Ardalan Mansouri , Mir Davood Omrani
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引用次数: 31

Abstract

Background

Ovarian cancer as the most lethal gynecologic malignancy in women is poorly detected during early stages of carcinogenesis. Therefore, there is an emergent need to look for specific and sensitive biomarkers for early diagnosis of ovarian cancer.

Materials and Methods

In this study, we performed real-time polymerase chain reaction (PCR) to evaluate the expression of six proapoptotic genes, CASP8, BAK, APAF1, BAX, BID, and BAD, which contain CpG islands in their promoter regions. Afterward, the significantly downregulated genes were investigated by HpaII-PCR and methylation-specific PCR (MSP) to determine the methylation status between tumoral and adjacent normal tissues.

Results

The real-time PCR results in 24 tumoral and 9 normal adjacent tissues showed decreased expression of CASP8 and BAD genes in tumoral relative to normal samples. Furthermore, the methylation analysis showed no significant methylation between tumoral and normal samples.

Conclusion

Taken together, this could be concluded that downregulation of CASP8 and BAD genes in ovarian cancer may be as important causes for ovarian cancer carcinogenesis via inducing resistance to apoptosis; however, the downregulations are not due to promoter hypermethylation.

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促凋亡基因Caspase-8-和bcl2相关细胞死亡激动剂在卵巢癌中的表达降低
背景:卵巢瓦癌是女性最致命的妇科恶性肿瘤,在癌变的早期很少被发现。因此,迫切需要寻找特异性和敏感性的生物标志物用于卵巢癌的早期诊断。材料与方法本研究采用实时聚合酶链反应(real-time polymerase chain reaction, PCR)检测了6个促凋亡基因CASP8、BAK、APAF1、BAX、BID和BAD的表达情况,这些基因的启动子区域均含有CpG岛。随后,通过hpai -PCR和甲基化特异性PCR (MSP)研究了显著下调的基因,以确定肿瘤和邻近正常组织之间的甲基化状态。结果24例肿瘤组织和9例正常癌旁组织的实时PCR结果显示,肿瘤组织中CASP8和BAD基因的表达较正常组织低。此外,甲基化分析显示肿瘤和正常样本之间没有显著的甲基化。结论CASP8和BAD基因在卵巢癌中的下调可能通过诱导细胞凋亡抵抗而成为卵巢癌发生的重要原因;然而,下调不是由于启动子超甲基化。
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WITHDRAWN: Epigenetic Pathways Offer Targets for Ovarian Cancer Treatment Table of Contents Editorial Board A Simulation Study of the Factors Influencing the Risk of Intraoperative Slipping Genetic Cancer Ovary
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