BACKGROUND: The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated and hormone-independent tumors. The gain of hormone independency over time even in estrogen receptor-positive tumors has become another obstacle to endocrine therapy for breast cancer. We tried to regain the hormone dependency in estrogen receptor-negative breast cancer cells by lipofecting estrogen receptor cDNA. MATERIALS AND METHODS: The mutant human estrogen receptor cDNA (pSG5-HE0) was lipofected into estrogen receptor-negative human breast cancer cell line MDA-MB-231, in an attempt to restore their sensitivity to antiestrogen. Then the effects if 17 beta -estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together. RESULTS: The cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that days. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly strong over combined conditions of tamoxifen and 17 beta estradiol compared to estrogen-treated group and to control. CONCLUSIONS: The temporary induction of estrogen receptor by lipofection with pSG5-HE0 on estrogen receptor-negative human breast cancer cell line MDA-MB-231 showed negative growth control on these cells by tamoxifen, indicating that liposome-mediated estrogen receptor transfection may be used as a novel therapeutic strategy for hormone independent human breast cancers in the near future.