Similar Datasets
Project description:Despite advances in cancer therapy, drug resistance remains a major obstacle in a range of cancer types, often driven by overexpression of ATP-binding cassette (ABC) transporters that restrict intracellular drug accumulation. Our previous studies identified the BRG1-p300 transcriptional complex at the promoters of specific ABC transporter genes. We used basal and induced doxorubicin-resistant triple-negative breast cancer (TNBC) cell lines to analyze changes in ABC transporter expression and drug accumulation following PARP1 inhibition. Moreover, the effect of commonly used antioxidants on the repressive effect of Veliparib against ABC genes was verified. ChIP-Seq was performed to identify transcription factor mediating PARP1-dependent ABC gene regulation. PARP1 inhibition or silencing of PARP1/HPF1 complex components downregulated ABCC and ABCG2 transporters, leading to increased intracellular accumulation of chemotherapeutic drugs in doxorubicin-resistant cells. Notably, suppression of genotoxic stress via antioxidant treatment reverses the inhibitory effect of Veliparib on ABC transporter expression. We identified SMARCA1 as a key regulator of PARP1-dependent expression of ABCC genes. SMARCA1 is a key effector of PARP1/p300-mediated regulation of ABC transporters and represents a potential therapeutic target in doxorubicin-resistant TNBC. These findings support the development of combinatorial strategies involving PARP1 inhibitors and chromatin remodeling modulators in refractory breast cancers.
2025-12-04 | GSE312254 | GEO
Project description:Despite advances in cancer therapy, drug resistance remains a major obstacle in a range of cancer types, often driven by overexpression of ATP-binding cassette (ABC) transporters that restrict intracellular drug accumulation. Our previous studies identified the BRG1-p300 transcriptional complex at the promoters of specific ABC transporter genes. We used basal and induced doxorubicin-resistant triple-negative breast cancer (TNBC) cell lines to analyze changes in ABC transporter expression and drug accumulation following PARP1 inhibition. Moreover, the effect of commonly used antioxidants on the repressive effect of Veliparib against ABC genes was verified. ChIP-Seq was performed to identify transcription factor mediating PARP1-dependent ABC gene regulation. PARP1 inhibition or silencing of PARP1/HPF1 complex components downregulated ABCC and ABCG2 transporters, leading to increased intracellular accumulation of chemotherapeutic drugs in doxorubicin-resistant cells. Notably, suppression of genotoxic stress via antioxidant treatment reverses the inhibitory effect of Veliparib on ABC transporter expression. We identified SMARCA1 as a key regulator of PARP1-dependent expression of ABCC genes. SMARCA1 is a key effector of PARP1/p300-mediated regulation of ABC transporters and represents a potential therapeutic target in doxorubicin-resistant TNBC. These findings support the development of combinatorial strategies involving PARP1 inhibitors and chromatin remodeling modulators in refractory breast cancers.
2025-12-04 | GSE312249 | GEO
Project description:Cupriavidus metallidurans CH34 is a well-studied metal-resistant β-proteobacterium and contains a battery of genes involved in the resistance and processing of numerous metals. Here, we performed a directed evolution experiment to obtain derivatives adapted to grow in the presence of zinc at concentrations above the minimal inhibitory concentration for the parental strain. Genetic characterization of one derivative, CH34ZnR, which was also more resistant to cadmium, revealed seven mutations, including inactivation of glpR coding for a DeoR-type transcriptional repressor by insertion of IS1088. The latter resulted in the constitutive expression of the neighboring ABC-type transporter. GlpR and the adjacent ABC transporter are highly similar to the glycerol operon regulator and ATP-driven glycerol importer of Rhizobium leguminosarum bv. viciae VF39, respectively. Deletion of glpR or the ABC transporter and complementation of CH34ZnR with the parental glpR gene further demonstrated that loss of GlpR function, with concomitant induction of the adjacent ABC transporter, is pivotal in the observed phenotype. Moreover, addition of glycerol, presumably by glycerol-mediated reduced GlpR activity, also promoted increased zinc and cadmium resistance. Thus, the ABC-type transporter is proposed to be a new adaptation route during exposure to toxic zinc concentrations.
2021-03-03 | GSE156826 | GEO
Project description:Comparative transcriptome analysis revealed that higher expressions of several metal transporter genes (ABC transporters, K+ transporters/channels, yellow stripe-like proteins, Zinc regulated transporter/iron-regulated transporter-like proteins, etc.) are involved in root uptake and translocation capacity in HCW
2020-01-08 | GSE143216 | GEO
Project description:ATP-binding cassette (ABC) transporters can translocate a broad spectrum of molecules across the cell membrane including physiological cargo and toxins. ABC transporters are known for the role they play in resistance towards anticancer agents in chemotherapy of cancer patients. There are 68 ABC transporters annotated in the genome of the social amoeba Dictyostelium discoideum. We have characterized more than half of these ABC transporters through a systematic study of mutations in their genes. We have analyzed morphological and transcriptional phenotypes for these mutants during growth and development and found that most of the mutants exhibited rather subtle phenotypes. A few of the genes may share physiological functions, as reflected in their transcriptional phenotypes. Since most of the abc-transporter mutants showed subtle morphological phenotypes, we utilized these transcriptional phenotypes to identify genes that are important for development by looking for transcripts whose abundance was unperturbed in most of the mutants. We found a set of 668 genes that includes many validated D. discoideum developmental genes. We have also found that abcG6 and abcG18 may have potential roles in intercellular signaling during terminal differentiation of spores and stalks. Transcriptional phenotyping during development of abc transporter mutants in Dictyostelium discoideum
2013-06-14 | E-GEOD-45555 | biostudies-arrayexpress
Project description:Since, ABC transporters do perform various physiological roles.To get better insight about possible involvement of putative ABC transporter orf19.4531 in different functions transcriptional profiling have been peformed and compared between WT(SC5314) Candida albicans cells vs putative orf19.4531 knockout cells after 6hrs growth of culture.The assay as peformed in biological duplicate sample.
2017-12-31 | GSE70340 | GEO
Project description:Inventory of ABC transporters of Candida albicans shows presence of large no of ABC transporters in its genome.The large no of such protein presence suggested that these proteins may involve in various functions.To know involvement of PM ABC transporter orf19.3120 in different physiological roles transcriptional profiling have been peformed and compared between WT(SC5314) Candida albicans cells vs orf19.3120 knockout cells after 6hrs growth of culture.The assay as peformed in biological duplicate sample.
2021-12-31 | GSE70339 | GEO
Project description:Recent reports have been suggested involvement of ABC transporters in various physiological roles.To get better insight about possible involvement of vacuolar ABC transporter MLT1/orf19.5100 in different physiological roles transcriptional profiling have been peformed and compared between WT(SC5314) Candida albicans cells vs putative orf19.5100 knockout cells after 6hrs growth of culture.The assay as peformed in biological duplicate sample.
2016-07-25 | GSE70341 | GEO
Project description:To determine the pleiotropic effect of the ABC transporter gene (Atpdr2) mutation, we performed the microarray analyses on the root tissues of Arabidopsis thaliana wild type (Col-0) and Atpdr2 mutant.
2009-10-20 | E-TABM-821 | biostudies-arrayexpress