Tamoxifen induces regression of estradiol-induced mammary cancer in the ACI.COP-Ept2 rat model.
The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5-7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonance imaging, by 89%. Tumors expressed estrogen receptors (ER), progesterone receptor (PR), and Erbb2. ERalpha and PR were overexpressed in tumor compared to adjacent non-tumor mammary gland. Thus, this model is highly relevant to hormone responsive human breast cancers.
Ruhlen
Rachel L
RL
Department of Surgery, University of Missouri-Columbia, One Hospital Drive, Rm N510, Columbia, MO 65212, USA.
Willbrand
Dana M
DM
Besch-Williford
Cynthia L
CL
Ma
Lixin
L
Shull
James D
JD
Sauter
Edward R
ER
D000818:Animals; D020296:Animals, Congenic; D004195:Disease Models, Animal; D004958:Estradiol / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*
D004958:Estradiol; D004967:Estrogens; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C508053:ERBB2 protein, human