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乳腺癌中Bax和Bak基因突变及表达的评估

Evaluation of Bax and Bak gene mutations and expression in breast cancer.

作者信息

Kholoussi Naglaa Mohamed, El-Nabi Sobhy E H, Esmaiel Nora Nassef, Abd El-Bary Naser Mohamed, El-Kased Ahmed F

机构信息

Immunogenetics, National Research Centre, Cairo 11516, Egypt.

Faculty of Science, Minufiya University, Menufia, Egypt.

出版信息

Biomed Res Int. 2014;2014:249372. doi: 10.1155/2014/249372. Epub 2014 Feb 9.

DOI:10.1155/2014/249372
PMID:24672785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3933335/
Abstract

Genetic analyses have provided evidence to suggest that Bax and Bak are the essential genes for apoptosis in mammalians cells. This study aimed to search for biomarkers in breast cancer to be used as prognostic markers for the disease. The Bak and Bax genes expressions were analyzed in 23 breast cancer patients by RT-PCR technique. SSCP technique was used to detect the mobility of the abnormal fragment in Bak exon 4. PCR for Bax promoter was digested with Tau 1 restriction enzyme to identify a single polymorphism G(-248)A. The expression of Bak gene is related to several clinical factors of breast cancer. The analysis of Bax RNA showed 4 isoforms of Bax with different distributions in the normal and tumor tissues. These isoforms were Bax α , d, δ , and ζ . Exon 4 had a normal pattern in all cases of breast cancer. There was a statistically significant difference in the frequency distribution of the G(-248)A genotypes in the breast cancer tissues with grade 3+high, T2 stage, lobular +other, and PR -ve subgroups. In this study, Bak expression seems to lead to development of breast cancer and affects the disease progression. Also, Bax d and Bax δ could be used as risk factor and biomarker for breast cancer with the distribution of G284A.

摘要

基因分析已提供证据表明，Bax和Bak是哺乳动物细胞凋亡的关键基因。本研究旨在寻找乳腺癌中的生物标志物，用作该疾病的预后标志物。采用RT-PCR技术分析了23例乳腺癌患者的Bak和Bax基因表达。运用SSCP技术检测Bak外显子4中异常片段的迁移率。用Tau 1限制性内切酶消化Bax启动子的PCR产物，以鉴定一个单核苷酸多态性G(-248)A。Bak基因的表达与乳腺癌的几个临床因素相关。Bax RNA分析显示，在正常组织和肿瘤组织中，Bax有4种不同分布的异构体，分别为Baxα、d、δ和ζ。在所有乳腺癌病例中，外显子4均呈正常模式。在3级以上、T2期、小叶型+其他类型以及孕激素受体阴性亚组的乳腺癌组织中，G(-248)A基因型的频率分布存在统计学显著差异。在本研究中，Bak表达似乎导致乳腺癌的发生并影响疾病进展。此外，Bax d和Baxδ可作为G284A分布型乳腺癌的危险因素和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/6dea0523e501/BMRI2014-249372.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/b68b31f6ad7c/BMRI2014-249372.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/3a01ec3e5a3a/BMRI2014-249372.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/c56d38b7fa0c/BMRI2014-249372.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/09c9aabb8200/BMRI2014-249372.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/6dea0523e501/BMRI2014-249372.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/b68b31f6ad7c/BMRI2014-249372.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/3a01ec3e5a3a/BMRI2014-249372.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/c56d38b7fa0c/BMRI2014-249372.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/09c9aabb8200/BMRI2014-249372.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4b/3933335/6dea0523e501/BMRI2014-249372.005.jpg

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