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高危型人乳头瘤病毒感染的卵巢癌中SFRPs和APC基因的甲基化

Methylation of SFRPs and APC genes in ovarian cancer infected with high risk human papillomavirus.

作者信息

Al-Shabanah Othman Abdulla, Hafez Mohamed Mahmoud, Hassan Zeinab Korany, Sayed-Ahmed Mohamed Mohamed, Abozeed Waleed Nabeel, Alsheikh Abdulmalik, Al-Rejaie Salem Saleh

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(6):2719-25. doi: 10.7314/apjcp.2014.15.6.2719.

Abstract

BACKGROUND

Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus.

MATERIALS AND METHODS

DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes.

RESULTS

The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression.

CONCLUSION

This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

摘要

背景

分泌型卷曲相关蛋白(SFRP)基因作为新的肿瘤抑制基因,是Wnt信号通路的负调控因子,其改变与多种肿瘤相关。在卵巢癌中,SFRP基因启动子甲基化可导致基因失活。本研究调查了高危型人乳头瘤病毒感染的卵巢癌中SFRP和腺瘤性息肉病基因(APC)沉默的机制。

材料与方法

从200例福尔马林固定石蜡包埋的卵巢癌组织及其正常相邻组织(NAT)中提取DNA,采用甲基化特异性PCR(MSP)检测DNA甲基化。采用巢式PCR和共有引物检测高危型人乳头瘤病毒(HPV),以扩增多种HPV基因型。

结果

与NAT相比,高危型HPV感染的卵巢癌组织中SFRP和APC基因的甲基化百分比显著更高。甲基化的研究基因与其基因表达的抑制相关。

结论

这一发现突出了高危型HPV病毒在卵巢癌发生过程中或通过DNA甲基化抑制SFRP和APC基因促进癌症进展中可能发挥的作用。

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