title: Synergistic effects of combined DNA methyltransferase inhibition and MBD2 depletion on breast cancer cells; MBD2 depletion blocks 5-aza-2'-deoxycytidine-triggered invasiveness.
abstract: 5-Aza-2'-deoxycytidine (5-azaCdR) not only inhibits growth of non-invasive breast cancer cells but also increases their invasiveness through induction of pro-metastatic genes. Methylated DNA binding protein 2 (MBD2) is involved in silencing methylated tumor suppressor genes as well as activation of pro-metastatic genes. In this study, we show that a combination of MBD2 depletion and DNA methyltransferases (DNMT) inhibition in breast cancer cells results in a combined effect in vitro and in vivo, enhancing tumor growth arrest on one hand, while inhibiting invasiveness triggered by 5-azaCdR on the other hand. The combined treatment of MBD2 depletion and 5-azaCdR suppresses and augments distinct gene networks that are induced by DNMT inhibition alone. These data point to a potential new approach in targeting the DNA methylation machinery by combination of MBD2 and DNMT inhibitors.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University and.
authors.forename: David
authors.initials: D
authors.lastname: Cheishvili
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University and.
authors.forename: Flora
authors.initials: F
authors.lastname: Chik
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University and.
authors.forename: Chen Chen
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University and Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada, McGill Centre for Bioinformatics, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec H3G 0B1, Canada and.
authors.forename: Bishnu
authors.initials: B
authors.lastname: Bhattacharya
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University and Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada, McGill Centre for Bioinformatics, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec H3G 0B1, Canada and.
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.affiliation: Department of Medicine, McGill University Health Centre, 687 Pine Avenue West, Room H4.67, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Ani
authors.initials: A
authors.lastname: Arakelian
authors.affiliation: McGill Centre for Bioinformatics, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec H3G 0B1, Canada and.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
authors.affiliation: Department of Medicine, McGill University Health Centre, 687 Pine Avenue West, Room H4.67, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Shafaat A
authors.initials: SA
authors.lastname: Rabbani
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University and Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada, moshe@szyfco.com.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C489325:MBD2 protein, human; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine