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- _6 value "More recently, ERBB transactivation has been shown to involve other physiological ligands (FIG. 2). The binding of WNT to its seven-pass membrane receptor Frizzled (FZD) transactivates EGFR. The mechanism seems to be similar to that described for GPCRs, as it is rapid and blocked by metalloproteinase inhibitors; however, the target ligand has not been identified. WNT?FZD-mediated transactivation has been observed in normal mammary cells43 and in breast cancer cells (T. Schlange and N.E.H., unpublished observations). Oestradiol (E2) bindingto plasma-membrane-associated oestrogen receptor (ER) has also been shown to rapidly transactivate ERBBs. According to one report, E2-stimulated activation of MMP2 and MMP9 leads to the release of HB-EGF. Tamoxifen, a selective ER modifier (SERM) was shown to transactivate EGFR and ERBB2, and in ERBB2-overexpressing breast cancer cells this reduced the antiproliferative activity of the SERM" provenance.
- _6 wasQuotedFrom 15864276 provenance.