Models of hormone resistance in vitro and in vivo.

Estrogen receptor (ER)-positive MCF-7 breast cancer cell lines can be used both in vitro and in vivo to create anti-hormone resistance. Estrogen withdrawal in vitro results in spontaneous growth of MCF-7 cells. Similarly, culture in the selective ER modulators (SERMs) tamoxifen and raloxifene, can result in SERM resistance. This form of anti-hormone resistance is evidenced by SERM-stimulated tumor growth in athymic mice. These tumors are transplantable into successive generations of overiectomized SERM treated mice. However, there is an evolution of drug resistance to anti-hormones. This is evidenced by a change in sensitivity to estrogen. The natural hormone no longer stimulated tumor growth but causes apoptosis and tumor regression.