Dexamethasone decreases expression of Aquaporin 5 in mouse mammary gland cells
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During normal mammary gland differentiation the membrane water channel aquaporin 5 (AQP5) is down-regulated. This is not the case in breast carcinomas in which high levels of AQP5 have been observed. In addition, an elevated AQP5 expression has been linked to cell proliferation and migration of breast cancer cells and it has been suggested that AQP5 plays a role in tumor progression. In this context, finding agents that regulate AQP5 expression could provide novel treatments for breast cancer. A potential candidate is the steroid hormone Dexamethasone (Dex), a drug already tested in AQP5 expression in asthma and shown to induce mammary tissue differentiation in an in vitro system. In this work, we explored the effect of Dex on AQP5 expression at the mRNA and protein level in mammary tissue using mouse mammary gland epithelial cells EpH4 as a model system. A 4-6 fold decrease of the AQP5 mRNA was observed already after 2 hours when treating polarized or confluent EpH4 cells with Dex. Protein levels also decreased, but with a delay of several hours compared to mRNA expression. No further decrease was observed for longer treatment periods. The decrease in expression levels of AQP5 was not coupled to changes in AQP5 promoter methylation. The division activity of the cells was observed to influence the strength of AQP5 down-regulation by Dex, with the strongest effect in non-dividing, polarized cells and an attenuated effect in actively dividing cells. Our results suggest that Dex could reduce AQP5 in mammary tissue by directly affecting AQP5 transcription. We discuss the role of nGRE receptors found ubiquitously in the AQP5 promoter as potential targets of Dex in the regulation of AQP5.