Hopeful
03-11-2011, 08:12 AM
The results showed that while the anti-hormonal suppressed ER, it simultaneously sensitized the cells to growth factor signaling.
http://breast-cancer-research.com/content/pdf/bcr2848.pdf
"Conclusions
These current findings demonstrate that targeting ER signalling with the pure antioestrogen fulvestrant can both suppress and induce gene and protein expression in ER-positive ErbB2-low and -overexpressing breast cancer cell lines. As expected fulvestrant was a potent growth inhibitor in all four of these ER-positive breast cancer cell lines through its ability to suppress proliferation-related genes such as cyclin D1. However, the simlutaneous induction of ErbB3 and ErbB4 also provided a mechanism for these cells, when in a HRG Beta 1-enriched environment, to promote re-expression of cyclin D1 and ultimately drive resistant cell growth. What is more fulvestrant treatment converted HRG Beta 1 from a ligand with both growth promoting and suppressive activity, depending on cell type, into one that consistently and potently promoted cell growth, regardless of ErbB2 status. Thus, although anti-hormones, such as fulvestrant, may have potent acute grwoth inhibitory activity in ER-positive breast cancer cells their ability to rapidly induce and sensitize cells to growth factors, such as heregulins, may serve to reduce and ultimately limit their inhibitory activity. Indeed, such a rapid induction of these proliferative genes may provide a mechanism of de novo endocrine resistance in situations where heregulin expression in the tumor microenvironment is high."
Hopeful
http://breast-cancer-research.com/content/pdf/bcr2848.pdf
"Conclusions
These current findings demonstrate that targeting ER signalling with the pure antioestrogen fulvestrant can both suppress and induce gene and protein expression in ER-positive ErbB2-low and -overexpressing breast cancer cell lines. As expected fulvestrant was a potent growth inhibitor in all four of these ER-positive breast cancer cell lines through its ability to suppress proliferation-related genes such as cyclin D1. However, the simlutaneous induction of ErbB3 and ErbB4 also provided a mechanism for these cells, when in a HRG Beta 1-enriched environment, to promote re-expression of cyclin D1 and ultimately drive resistant cell growth. What is more fulvestrant treatment converted HRG Beta 1 from a ligand with both growth promoting and suppressive activity, depending on cell type, into one that consistently and potently promoted cell growth, regardless of ErbB2 status. Thus, although anti-hormones, such as fulvestrant, may have potent acute grwoth inhibitory activity in ER-positive breast cancer cells their ability to rapidly induce and sensitize cells to growth factors, such as heregulins, may serve to reduce and ultimately limit their inhibitory activity. Indeed, such a rapid induction of these proliferative genes may provide a mechanism of de novo endocrine resistance in situations where heregulin expression in the tumor microenvironment is high."
Hopeful