Abstract: Objective: To investigate the relationship between amphiregulin expression and uPA production in a human breast cancer model. Methods: Human amphiregulin cDNA antisense plasmid was transfected in NS2T2A1 cells. Two clones, selected by hygromycin B, expressed AR antisense RNA (AR AS1 and AR AS3 cell lines) in which AR protein expression was reduced. Control cell line NS2T2A1 V was obtained by empty vector transfection. These cells were injected subcutaneously in nude mice to obtain tumors. The in vitro and in vivo uPA production were detected, and the correlation between uPA expression and invasive capability of tumor cells was studied. Results: The in vitro and in vivo uPA expression were inhibited in AR AS1 and AR AS3 cells in comparison with that of the control cells. Exogenous amphiregulin stimulated uPA production in control cells and partially restored the uPA level in AS1 and AR AS3 cells. Amphiregulin cDNA antisense transfection as well as anti-uPA antibody treatment suppressed the invasive capability of tumor cell. Conclusion: The uPA expression is closely related with tumor cell invasion in the breast cancer model. Amphiregulin antisense RNA expression can efficiently inhibit uPA production and the invasive capability of tumor cell.