dataset
posted on 2023-04-03, 18:27 authored by Margaret L. Dahn, Brianne M. Cruickshank, Ainsleigh J. Jackson, Cheryl Dean, Ryan W. Holloway, Steven R. Hall, Krysta M. Coyle, Hillary Maillet, David M. Waisman, Kerry B. Goralski, Carman A. Giacomantonio, Ian C.G. Weaver, Paola Marcato Microarray gene expression analyses for MDA-MB-468, MDA-MB-231, and SUM159 cells after decitabine treatment
Funding
Cancer Research Society
Institute of Cancer Research
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada
CIHR
Nova Scotia Health Research Foundation
Killam Laureate scholarship
Nova Scotia Research and Innovation Graduate
Killam Laureate scholarships
Dalhousie Medical Research Foundation
TCGA Research Network
History
ARTICLE ABSTRACT
Dysregulation of DNA methylation is an established feature of breast cancers. DNA demethylating therapies like decitabine are proposed for the treatment of triple-negative breast cancers (TNBC) and indicators of response need to be identified. For this purpose, we characterized the effects of decitabine in a panel of 10 breast cancer cell lines and observed a range of sensitivity to decitabine that was not subtype specific. Knockdown of potential key effectors demonstrated the requirement of deoxycytidine kinase (DCK) for decitabine response in breast cancer cells. In treatment-naïve breast tumors, DCK was higher in TNBCs, and DCK levels were sustained or increased post chemotherapy treatment. This suggests that limited DCK levels will not be a barrier to response in patients with TNBC treated with decitabine as a second-line treatment or in a clinical trial. Methylome analysis revealed that genome-wide, region-specific, tumor suppressor gene–specific methylation, and decitabine-induced demethylation did not predict response to decitabine. Gene set enrichment analysis of transcriptome data demonstrated that decitabine induced genes within apoptosis, cell cycle, stress, and immune pathways. Induced genes included those characterized by the viral mimicry response; however, knockdown of key effectors of the pathway did not affect decitabine sensitivity suggesting that breast cancer growth suppression by decitabine is independent of viral mimicry. Finally, taxol-resistant breast cancer cells expressing high levels of multidrug resistance transporter ABCB1 remained sensitive to decitabine, suggesting that the drug could be used as second-line treatment for chemoresistant patients.
