Dataset Information

Short term exposure to alcohol induces transcriptional changes in non-tumorigenic breast cells

ABSTRACT: Breast cancer is the second leading cause of cancer-related deaths in women (*). Many genetic and behavioral risk factors can contribute to the initiation and progression of breast cancer, one being alcohol consumption. Numerous epidemiological studies have established a positive correlation between alcohol consumption and breast cancer; however, the molecular basis for this link remains ill defined. Elucidating ethanol-induced changes to global transcriptional programming in breast cells is important to ultimately understand how alcohol and breast cancer are connected mechanistically. We investigated early induced transcriptional changes in response to cellular exposure to moderate levels of alcohol. We treated the non-tumorigenic breast cell line MCF10A, and the tumorigenic breast cell lines MDA-MB-231 and MCF7, with ethanol for 6 h, then captured the changes to ongoing transcription using 4-thiouridine metabolic labeling followed by deep sequencing. Only the MCF10A cell line exhibited statistically significant changes to ongoing transcription in response to ethanol treatment. Further experiments revealed some ethanol-upregulated genes are sensitive to the dose of alcohol treatment, while others are not. Gene ontology and biochemical pathway analyses revealed that ethanol-upregulated genes in MCF10A cells are enriched in biological functions that could contribute to cancer development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221280 | GEO | 2023/08/04

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Despite recent extensive genomic and genetic studies on behavioral responses to ethanol, relatively few new therapeutic targets for the treatment of alcohol use disorder have been validated. Here we describe a cross-species genomic approach focused on identifying gene networks associated with chronic ethanol consumption. To identify brain mechanisms underlying a chronic ethanol consumption phenotype highly relevant to human alcohol use disorder, and to elucidate potential future therapeutic targets, we conducted a genomic study in a nonhuman primate model of chronic open-access ethanol consumption. Microarray analysis of RNA expression in anterior cingulate and subgenual cortices from rhesus macaques was performed across multiple cohorts of animals. Gene networks correlating with ethanol consumption or showing enrichment for ethanol-regulated genes were identified, as were major ethanol-related hub genes within these networks. A subsequent consensus module analysis was used to co-analyze monkey data with expression data from a chronic intermittent ethanol vapor-exposure and consumption model in C57BL/6J mice. Ethanol-related gene networks conserved between primates and rodents were enriched for genes involved discrete biological functions, including; myelination, synaptic transmission, chromatin modification, Golgi apparatus function, translation, cellular respiration, and RNA processing. The myelin-related network, in particular, showed strong correlations with ethanol consumption behavior and displayed marked network reorganization between control and ethanol-drinking animals. Further bioinformatics analysis revealed that these networks also showed highly significant overlap with other ethanol-regulated gene sets. Altogether, these studies provide robust primate and rodent cross-species validation of gene networks associated with chronic ethanol consumption. Our results also suggest potential novel focal points for future therapeutic interventions in alcohol use disorder.

Dataset Information

Short term exposure to alcohol induces transcriptional changes in non-tumorigenic breast cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets