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Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Manitoba, R3E 0W3 Canada
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-
(ER-). 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.
1 This work was supported by the United States Army Medical Research and Materiel Command, the Medical Research Council of Canada, and the Manitoba Health Research Council. L. C. M. is a Medical Research Council of Canada Scientist, and A. S. C. holds a Manitoba Health Research Council Studentship.
2 To whom requests for reprints should be addressed. Phone: (204) 789-3233; Fax: (204) 789-3900; E-mail: lcmurph@cc.umanitoba.ca.
Received 6/29/98. Accepted 7/27/98.
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