T47D breast cancer cells switch from ER/HER to HER/c-Src signaling upon acquiring resistance to the antiestrogen fulvestrant

• Two new fulvestrant resistant T47D breast cancer cell lines are investigated.
• The resistant cell lines have a stable ER-negative/HER2 over expressing phenotype.
• HER2 targeted therapy has no effect on resistant cell growth.
• A pan-HER inhibitor abrogates both parental and resistant cell growth.
• c-Src plays a major role for resistant growth.

In this study, T47D cell lines resistant to the antiestrogen fulvestrant were established and analyzed to explore, whether a switch to HER signaling, as seen in fulvestrant resistant MCF-7 cell lines, is a general resistance mechanism. We find that parental T47D cells depend on ER and HER signaling for growth. Fulvestrant resistant T47D cells have lost ER expression and, although HER2 was over expressed, growth was only partially driven by HER receptors. Instead c-Src was important for resistant growth. Thus, the T47D and MCF-7 model system unravel different resistance mechanisms which may be important for fulvestrant resistant breast cancer patients.