Alcohol increases cell proliferation in an estrogen-dependent manner, promotes the activation of ERK1/2, as well as known ER target genes.

<p>(A), Trypan blue exclusion assays demonstrate that estrogen potentiates cell proliferation increases by alcohol. DMSO treated cells are not statistically different from DMSO and alcohol cotreatment. (B), MTS assays measure statistically significant increases in metabolic rate at 21.7, 43.4 and 65.1 mmol/L ethanol concentrations. Treatment with 86.8 mmol/L EtOH did not result in an increase in cell proliferation. (C) Alcohol promotes the phosphorylation of ERK1/2, a key effector of growth factor signaling and of G1-S progression, regardless of estrogen treatment. Quantification comprises data of experiments in triplicate. (D) The effect of alcohol was tested on ER responsive genes TFF1/pS2 and GREB1 in MCF-7 cells. Only GREB1 responds to alcohol treatment, suggesting a possible overlap between cellular estrogen signaling and alcohol response.