Elevated mitogen-activated protein kinase activity in estrogen-nonresponsive human breast cancer cells.
The mitogen-activated protein kinase (MAPK) signal transduction pathway plays an essential role in cell cycle progression and can be activated by many growth factor/mitogen pathways including estrogen. MAPK has also been implicated in ligand-independent activation of estrogen receptor-alpha (ER-alpha). The development of estrogen-independent growth in breast cancer is likely a first step in progression to hormone independence and antiestrogen resistance. We examined MAPK expression and activity in T5-PRF and T5 human breast cancer cells. T5-PRF is an estrogen-nonresponsive cell line developed from T5 cells by chronically depleting the cells of estrogen in long-term culture. MAPK activity measured 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 estrogen nonresponsive growth phenotype and ligand-independent activity of ER in T5-PRF cells.
Coutts
A S
AS
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
Murphy
L C
LC
D001943:Breast Neoplasms / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D009363:Neoplasm Proteins; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D004958:Estradiol; C051781:ICI 164384; D017871:Calcium-Calmodulin-Dependent Protein Kinases