Abstract
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-α (ER-α). 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.
Footnotes
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↵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.
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↵2 To whom requests for reprints should be addressed. Phone: (204) 789-3233; Fax: (204) 789-3900; E-mail: lcmurph@cc.umanitoba.ca.
- Received June 29, 1998.
- Accepted July 27, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 18
