17β-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells

In this study, we show that 17β-Estradiol (E2) induced the proliferation of T84 colonic carcinoma cells. We, further, investigated the mechanisms underlying this proliferation and show that E2 induced c-fos protooncogene expression in T84 cells in a timescale consistent with a rapid non-genomic action of the hormone. Furthermore, E2 rapidly phosphorylated both CREB and ELK1, transcription factors that bind to the c-fos promoter and stimulate transcription. Pretreatment with PD98059 and H89, mitogen-activated protein kinase (MAPK) pathway and protein kinase A (PKA) inhibitors, respectively showed that phosphorylation of CREB and ELK1 and subsequent c-fos induction was mediated by the MAPK pathway only. Finally, the estrogen receptor (ER) antagonist, ICI 182,780, blocked the activation of MAPK pathway, subsequent CREB and ELK1 phosphorylation and c-fos induction in T84 cells suggesting an ER dependent mechanism. Consistent with this finding, ICI 182,780 caused a substantial reduction in the proliferative effects of E2 on T84 cells.