HER2 Support Group Forums - View Single Post - Dramatic new approach: using Src inhibitors to turn ER- into ER+ tumors

Lani · 07-16-2007, 06:10 AM

Up to one-third of primary breast cancers show HER2/
erbB-2 amplification, and a similar proportion has
increased EGFR expression. Both are strongly associated
with ER?– status (52, 53). Transfection of either EGFR or
activated Her2 can reduce ER? levels in MCF-7 cells, and
this has been attributed to MAPK activation (54). How-
ever, both of these receptors activate Src. In breast cancer
cells, cSrc binds phosphorylated Her2 or EGFR, promot-
ing synergistic activation to stimulate breast cancer cell
proliferation and survival (49). Indeed, Src inhibitors
impair Her2- and EGFR-driven mitogenesis (49, 55). Src is
also transiently recruited to and activated by estrogen-bound ER?,
leading to MAPK activation (22–25).

07-16-2007, 06:10 AM	#2
Lani Senior Member Join Date: Mar 2006 Posts: 4,780	pertinent paragraph Up to one-third of primary breast cancers show HER2/ erbB-2 amplification, and a similar proportion has increased EGFR expression. Both are strongly associated with ER?– status (52, 53). Transfection of either EGFR or activated Her2 can reduce ER? levels in MCF-7 cells, and this has been attributed to MAPK activation (54). How- ever, both of these receptors activate Src. In breast cancer cells, cSrc binds phosphorylated Her2 or EGFR, promot- ing synergistic activation to stimulate breast cancer cell proliferation and survival (49). Indeed, Src inhibitors impair Her2- and EGFR-driven mitogenesis (49, 55). Src is also transiently recruited to and activated by estrogen-bound ER?, leading to MAPK activation (22–25).