ELEVATED MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVITY IN ESTROGEN-NONRESPONSIVE HUMAN BREAST-CANCER CELLS

The mitogen-activated protein kinase (MAPK) signal transduction pathwa y plays an essential role in cell cycle progression and can be activat ed by many growth factor/mitogen pathways including estrogen. MAPK has also been implicated in ligand-independent activation of estrogen rec eptor-alpha (ER-alpha). The development of estrogen-independent growth in breast cancer is likely a first step in progression to hormone ind ependence and antiestrogen resistance. We examined MAPK expression and activity in T5-PRF and T5 human breast cancer cells. T5-PRF is an est rogen-nonresponsive cell line developed from T5 cells by chronically d epleting the cells of estrogen in long-term culture. MAPK activity mea sured in vitro was significantly higher (P < 0.05) in T5-PRF compared with T5 cells. Western blot analyses showed increased levels of active dually phosphorylated MAPK in T5-PRF cell extracts compared with T5. The increased activity and expression of MAPK may contribute to the es trogen nonresponsive growth phenotype and ligand-independent activity of ER in T5-PRF cells.