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.
Robert H Lurie Comprehensive Cancer Center, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jennifer MacGregor
JM
Schafer
V Craig
VC
Jordan
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000378:metabolism; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000378:metabolism
D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D004958:Estradiol