Linowiecka Kinga, Urbanowska-Domańska Olga, Guz Jolanta, Foksiński Marek
Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland.
Department of Oncology, Professor Franciszek Lukaszczyk Oncology Centre, Bydgoszcz, Poland.
Contemp Oncol (Pozn). 2019;23(2):74-80. doi: 10.5114/wo.2019.85200. Epub 2019 May 27.
Alterations in DNA methylation may cause disturbances in regulation of gene expression, including drug metabolism and distribution. Moreover, many cancers, including breast cancer, are characterized by DNA hypomethylation and a decreased 5-hydroxymethylcytosine level. The abnormal cell growth found in breast carcinoma might be the result of impaired up-regulation of breast cancer receptors. Receptors' expression in breast cancer determines clinical outcome, and it is possible that they lead to different DNA methylation patterns. Excessive steroid exposure can affect DNA methylation by promoting demethylation of CpG islands in promoter regions of genes, and hence may have an impact on promotion and progression of breast cancer cells. Tamoxifen, as a leading drug in breast cancer hormone therapy, has an ability to act like estrogen or antiestrogen depending on the type and localization of the breast cancer receptor. Further studies are needed to determine whether tamoxifen, similarly to steroids, may evoke changes in methylation pattern.
DNA甲基化的改变可能会导致基因表达调控紊乱，包括药物代谢和分布。此外，许多癌症，包括乳腺癌，其特征是DNA低甲基化和5-羟甲基胞嘧啶水平降低。乳腺癌中发现的异常细胞生长可能是乳腺癌受体上调受损的结果。乳腺癌中受体的表达决定临床结果，并且它们有可能导致不同的DNA甲基化模式。过多的类固醇暴露可通过促进基因启动子区域CpG岛的去甲基化来影响DNA甲基化，因此可能对乳腺癌细胞的促进和进展产生影响。他莫昔芬作为乳腺癌激素治疗的主要药物，根据乳腺癌受体的类型和定位，具有类似雌激素或抗雌激素的作用。需要进一步研究以确定他莫昔芬是否与类固醇类似，可能引起甲基化模式的变化。
