Estrogen and Vitamin D Control of Transcription in MCF‐7 Cells

Abstract

The Extracellular Signal‐Regulated Kinase (ERK) is part of a key, signaling pathway that regulates both transcription and translation in many cell types. Increases in intracellular calcium levels results in the CaM Kinase‐dependent activation of ERK and cell growth in MCF‐7 breast cancer cells. ERK has also been shown to play a role in the regulation of MCF‐7 cell proliferation through control of downstream transcription factors including Elk‐1. The hormone, Vitamin D has been suggested to play an inhibitory role on cancer cells by blocking ERK activation. Our goal was to evaluate the ability of E2 to activate Elk‐1, through a CaM Kinase/ERK dependent pathway, in MCF‐7 cells. We also examined Vitamin D's inhibitory regulation of ERK and Elk‐1 activation. Interestingly, E2 stimulation of MCF‐7 cells triggered Elk‐1 phosphorylation an effect that was blocked by inhibiting either CaM KK or ERK. Similarly, E2 treatment of MCF‐7 cells also triggered a significant increase in Elk‐1‐dependent luciferase activity. siRNA inhibition of CaM KK or ERK blocked E2‐stimulated Elk‐1 luciferase activity. Additionally, E2 triggered a sustained increase in ERK and Elk‐1 phosphorylation, both of which were blocked by Vitamin D treatment. Vitamin D treatment of cells also inhibited Elk‐1 luciferase activity downstream of E2 stimulation. In summary, our data suggests that E2 utilizes both CaM KK and ERK to activate Elk‐1 transcriptional activity an effect that is blocked by the hormone Vitamin D.