Short‐term exposure to ethanol induces transcriptional changes in nontumorigenic breast cells

Abstract

Breast cancer is a 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 induced transcriptional changes in response to a short cellular exposure to moderate levels of alcohol. We treated the nontumorigenic breast cell line MCF10A and the tumorigenic breast cell lines MDA‐MB‐231 and MCF7, with ethanol for 6 h, and 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 in newly transcribed RNA in response to ethanol treatment. Further experiments revealed that 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.

Keywords

• 4sU‐seq
• alcohol
• breast cancer
• transcription