Insulin Like Growth Factor 1 Receptor Function in Estrogen Receptor Negative Breast Cancer

摘要

Estrogen receptor (ER) negative breast cancer is associated with perturbations of growth regulatory pathways. Three in vitro models of ER+ and ER- breast cancer were evaluated for expression and activation of MAP kinase. Despite decreased activation of MAP kinase in ER- cells, these cells are still dependent on MAP kinase to maintain normal proliferation as evidenced by the lack of proliferation in the presence of UO 126, a MAP kinase inhibitor. Data presented in this report demonstrates that inhibition of the PI-3 kinase pathway is only growth inhibitory for ER+ cells, further evidence of the importance of MAP kinase signaling for growth. A second MAP kinase family member, ERK 5, was evaluated for expression and activation by western blot. Two of the three ER- cell lines upregulate activation of ERKS, potentially through the erbB2 receptor, and ERK 5 activity was inhibited in the presence of UOl26 and LY294002. These results demonstrate upregulation of growth factor signaling pathways is critical for proliferation of ER- breast cancer cells and further validate the MAP kinase pathway as a target for therapeutic intervention.