Objective      To determine the effect of estrogen receptor α36 (ER-α36) on the sensitivity to Herceptin

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

in breast cancer cell lines.       Methods      G418 was used for the screening for ER-α36 over-expressing breast cancer cell line BT474/ER-α36 and control cell line BT474/V

and then the phenotype of the paired cells was identified by Western blotting. The sensitivity of the paired cells to Herceptin was observed in normal culture condition and in the presence or absence of estrogen (E2) by cell proliferation assay. Western blotting was used to detect the different phosphorylation levels of E2-induced Akt and MAPK in the paired cells before and after Heceptin treatment.       Results       ER-α36 over-expressing breast cancer cell line BT474/ER-α36 and control cell line BT474/V had been screened successfully. In normal culture condition

the inhibitory ratio of Herceptin on the proliferation of BT474/ER-α36 and BT474/V cells was (22.00±0.06)% and (42.00±0.06)%

respectively

indicating that the sensitivity of BT474/ER-α36 cells to Herceptin was obviously attenuated

compared with control cells (P0.01). In the presence of E2

the inhibitory ratio of Herceptin on the proliferation of BT474/ER-α36 and BT474/V cells deprived of steroid hormones was (34.00±0.06)% and (53.00±0.06)%

respectively

indicating that E2 significantly decreases the sensitivity of BT474/ER-α36 cells to Herceptin. E2-induced phosphorylation of Akt or MAPK

a downstream molecule of HER2 pathway

was up-regulated over 3.08 fold or 2.63 fold

in BT474/ER-α36 cells

but only was up-regulated over 2.37 fold or 1.72 fold

in BT474/V cells. Compared with BT474/V control cells

the higher E2-induced ERα-36 non genomic activities and the weaker inhibition of phosphorylation of Akt and MAPK caused by Herceptin were found in BT474/ER-α36 cells (P0.01).       Conclusion      ER-α36 can affect the sensitivity of breast cancer cells to Herceptin through non-genomic activity.