Epigenetic Changes of CXCR4 and Its Ligand CXCL12 as Prognostic Factors for Sporadic Breast Cancer
العنوان: | Epigenetic Changes of CXCR4 and Its Ligand CXCL12 as Prognostic Factors for Sporadic Breast Cancer |
---|---|
المؤلفون: | Fabricio F. Costa, Gerusa G. Seniski, Mariana Grochoski, Karin Braun-Prado, Iglenir J. Cavalli, Giseli Klassen, Anamaria A. Camargo, Edneia A.S. Ramos, Enilze Maria de Souza Fonseca Ribeiro |
المصدر: | PLoS ONE PLoS ONE, Vol 6, Iss 12, p e29461 (2011) |
بيانات النشر: | Public Library of Science (PLoS), 2011. |
سنة النشر: | 2011 |
مصطلحات موضوعية: | lcsh:Medicine, Invasive Ductal Carcinoma, Kaplan-Meier Estimate, Epigenesis, Genetic, Metastasis, Basic Cancer Research, Breast Tumors, Pathology, lcsh:Science, Promoter Regions, Genetic, Aged, 80 and over, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Methylation, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, Oncology, CpG site, DNA methylation, Medicine, Female, Epigenetics, Invasive Lobular Carcinoma, DNA modification, Brazil, Cancer Screening, Research Article, Adult, Receptors, CXCR4, Breast Neoplasms, Biology, Breast cancer, Diagnostic Medicine, Cell Line, Tumor, Pancreatic cancer, Genetics, Cancer Detection and Diagnosis, medicine, Humans, Gene Silencing, Aged, lcsh:R, Cancers and Neoplasms, Cancer, Sequence Analysis, DNA, DNA Methylation, medicine.disease, Chemokine CXCL12, Cancer research, lcsh:Q, Gene expression, Biomarkers, General Pathology |
الوصف: | Chemokines and their receptors are involved in the development and cancer progression. The chemokine CXCL12 interacts with its receptor, CXCR4, to promote cellular adhesion, survival, proliferation and migration. The CXCR4 gene is upregulated in several types of cancers, including skin, lung, pancreas, brain and breast tumors. In pancreatic cancer and melanoma, CXCR4 expression is regulated by DNA methylation within its promoter region. In this study we examined the role of cytosine methylation in the regulation of CXCR4 expression in breast cancer cell lines and also correlated the methylation pattern with the clinicopathological aspects of sixty-nine primary breast tumors from a cohort of Brazilian women. RT-PCR showed that the PMC-42, MCF7 and MDA-MB-436 breast tumor cell lines expressed high levels of CXCR4. Conversely, the MDA-MB-435 cell line only expressed CXCR4 after treatment with 5-Aza-CdR, which suggests that CXCR4 expression is regulated by DNA methylation. To confirm this hypothesis, a 184 bp fragment of the CXCR4 gene promoter region was cloned after sodium bisulfite DNA treatment. Sequencing data showed that cell lines that expressed CXCR4 had only 15% of methylated CpG dinucleotides, while the cell line that not have CXCR4 expression, had a high density of methylation (91%). Loss of DNA methylation in the CXCR4 promoter was detected in 67% of the breast cancer analyzed. The absence of CXCR4 methylation was associated with the tumor stage, size, histological grade, lymph node status, ESR1 methylation and CXCL12 methylation, metastasis and patient death. Kaplan-Meier curves demonstrated that patients with an unmethylated CXCR4 promoter had a poorer overall survival and disease-free survival. Furthermore, patients with both CXCL12 methylation and unmethylated CXCR4 had a shorter overall survival and disease-free survival. These findings suggest that the DNA methylation status of both CXCR4 and CXCL12 genes could be used as a biomarker for prognosis in breast cancer. |
تدمد: | 1932-6203 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6bdf1b0ad13392bffbb863c29fe56d6b https://doi.org/10.1371/journal.pone.0029461 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....6bdf1b0ad13392bffbb863c29fe56d6b |
قاعدة البيانات: | OpenAIRE |
تدمد: | 19326203 |
---|