Objective      To determine the effect of estrogen (E2) on the sensitivity of Herceptin

a humanized monoclonal antibody directed against human epidermal growth factor receptor 2 (HER2)

in ER positive breast cancer cell line and investigate the underlying mechanism of this effect whether through estrogen receptor (ER) non-genomic activity.     Methods      ER-positive/HER2-positive breast cancer BT-474 cells and ER-negative/HER2-positive SKBR-3 cells was identified by Western blotting and instantaneous carrying combined with fluorescent element enzymes. In the presence or absence of estrogen

the sensitivity of the cells to Herceptin on inhibiting Hereguilin-induced cell proliferation was detected by cell proliferation assay and the effect of Herceptin on the levels of phosphorylation of MAPK and the downstream key molecules of HER2 pathway  was observed by Western blotting.     Results      In absence of estrogen

Herceptin effectively inhibited Hereguilin-induced proliferation of BT-474 and SKBR-3 cells (P0.01). In presence of estrogen

the inhibitory effect of herceptin on Hereguilin-induced BT-474 cell proliferation was disappeared (P0.01) and Herceptin could not inhibit Hereguilin-induced phosphorylation of MAPK. These changes were not observed in SKBR-3 cells.     Conclusion       E2 can affect the efficiency of Herceptin on ER positive breast cancer cells through the ER non-genomic activity

which may be involved in the generation of Herceptin resistance.