Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer?
| Autor: | Ghasemali Khorasani, Pantea Izadi, Mohammad Mehdi Naghizadeh, Milad Bastami, Nahid Nafissi, Yaser Mansoori, Ziba Nariman-Saleh-Fam, Zahra Saadatian, Zahra Zendehbad, Alipasha Meysamie, Abdolreza Daraei, Nasim Younosi, Javad Tavakkoly-Bazzaz |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
0301 basic medicine Physiology Breast Neoplasms Progesterone Receptor Isoform A Biology Biochemistry Epigenesis Genetic Young Adult 03 medical and health sciences 0302 clinical medicine Breast cancer Progesterone receptor Biomarkers Tumor medicine Humans Breast Epigenetics Promoter Regions Genetic skin and connective tissue diseases Molecular Biology Menarche Cell Biology Methylation DNA Methylation Middle Aged medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology CpG site 030220 oncology & carcinogenesis DNA methylation CpG Islands Female Receptors Progesterone |
| Zdroj: | Journal of Cellular Biochemistry. 120:12393-12401 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.28505 |
| Popis: | Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform α is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR-α (progesterone receptor α) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR-α promoter CpG island was determined by using MeDIP-qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR-α promoter ( β = -0.790, SE = 0.362; P = 0.031). Although lactating women had more methylation than nonlactating women (P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes. |
| Databáze: | OpenAIRE |
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