Hopeful
06-29-2011, 06:39 AM
http://breast-cancer-research.com/content/pdf/bcr2913.pdf
Collectively, our observations in primary breast tumors and in breast cancer cells in vitro provide evidence that the overexpression of 14-3-3ζ and the associated 14-3-3ζ gene signature identify a subgroup of ER positive tumors most likely to be resistant to endocrine therapies and to show early recurrence. In addition, our studies reveal that 14-3-3ζ expression can also be increased as a consequence of tamoxifen treatment, and therefore, ironically, that tamoxifen itself, through up-regulation of 14-3-3ζ, may be contributing to the development of endocrine resistance.
Broad impact of 14-3-3ζ on key cellular activities and signaling pathways
14-3-3ζ status had a great impact on cell signaling pathways and the molecular properties of breast cancer cells. With high 14-3-3ζ, cells showed enhanced activation of EGFR, HER2, MAPK, and AKT, and increased anchorage-dependent and independent growth. These activities were suppressed by down-regulation of 14-3-3ζ. Thus, 14-3-3ζ increases signaling through a variety of growth factor receptors and protein kinase pathways, stimulating a more robust and temporally prolonged activation of these pathways to promote survival and anti-apoptotic signaling, and enhance the endocrine resistance of breast cancer cells.
Hopeful
Collectively, our observations in primary breast tumors and in breast cancer cells in vitro provide evidence that the overexpression of 14-3-3ζ and the associated 14-3-3ζ gene signature identify a subgroup of ER positive tumors most likely to be resistant to endocrine therapies and to show early recurrence. In addition, our studies reveal that 14-3-3ζ expression can also be increased as a consequence of tamoxifen treatment, and therefore, ironically, that tamoxifen itself, through up-regulation of 14-3-3ζ, may be contributing to the development of endocrine resistance.
Broad impact of 14-3-3ζ on key cellular activities and signaling pathways
14-3-3ζ status had a great impact on cell signaling pathways and the molecular properties of breast cancer cells. With high 14-3-3ζ, cells showed enhanced activation of EGFR, HER2, MAPK, and AKT, and increased anchorage-dependent and independent growth. These activities were suppressed by down-regulation of 14-3-3ζ. Thus, 14-3-3ζ increases signaling through a variety of growth factor receptors and protein kinase pathways, stimulating a more robust and temporally prolonged activation of these pathways to promote survival and anti-apoptotic signaling, and enhance the endocrine resistance of breast cancer cells.
Hopeful