Therapeutic doses of Tamoxifen only partially inhibit the non-genomic effects of Estrogen: Evidence for additive anti-proliferative effect of Tamoxifen with MEK inhibitor

Aims: Data suggests that non-genomic effects of Estradiol (E2) in estrogen-sensitive carcinoma cell lines result in the activation of the MAP-Kinase (MAPK) pathway (p44/42). MAPK activation is a potent proliferative stimulus and E2 activation of this cascade seems to occur rapidly at the plasma membrane. We investigated the interaction of the SERM Tamoxifen (Tam) and a MAPK inhibitor (MEK inhibitor PD98059) on the non-genomic effects of E2. Methods: MCF-7 cells were maintained in DMEM with 10% FCS. For proliferation experiments, cells were cultured into 96-well plates using seeding densities of 5000 cells /cm3.…