Invasion and metastasis are crucial steps in breast cancer for patient's survival. Recent studies suggest the involvement of loss of DNA methylation resulting in the activation of prometastatic genes, such as uPA and heparanase, during metastasis progression. Also, global DNA hypomethylation and regional DNA hypermethylation are associated with tumorigenesis. Methylated CpG binding protein 2 (MBD2) binds to methylated DNA and demethylates it. Early growth response 1 (EGR1) is also implicated in metastasis and DNA demethylation. We show in this study that MBD2 expression in breast cancer cell lines correlates with uPA expression. Moreover, MBD2 overexpression leads to a global DNA hypomethylation. Furthermore, MBD2 and EGR1 expression induces uPA promoter activity alone or in combination. We also demonstrate a physical interaction between EGR1 and uPA promoter as well as EGR1 and MBD2. Taken together, these data demonstrate that MBD2 in association with EGR1 regulates uPA gene expression through DNA demethylation, and involvement of MBD2 in regulation of metastasis progression.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101796 |
| Date | January 2006 |
| Creators | Shikimi, Keisuke. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | © Keisuke Shikimi, 2006 |
| Relation | alephsysno: 002585653, proquestno: AAIMR32860, Theses scanned by UMI/ProQuest. |
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