Mammary tumor development from T47-D human breast cancer cells in obese ovariectomized mice with and without estradiol supplements.
Obesity is a risk factor for postmenopausal breast cancer, particularly for development of estrogen-receptor (ER)-positive tumors. Additionally, obesity is implicated in breast cancer progression. However, few studies address mechanisms of action of how obesity mediates these responses. Our goal was to address how obesity and/or elevated serum leptin affects tumor formation from ER-positive T47-D cells. In Study 1 ovariectomized CD-1 nude female mice were injected with goldthioglucose (GTG) at 0.5 mg/g body weight in saline or the vehicle at 6 weeks of age. At 10 weeks of age mice were inoculated with T47-D cells and implanted with estrogen pellets. In Study 2 mice were injected with 0.3 mg/g GTG or the vehicle. At 10 weeks of age cells were inoculated and mice were implanted with estrogen or placebo pellets. Mice were followed until 30 weeks of age. Some GTG mice became obese and others were non-responders. In Study 1 no mice developed tumors. In Study 2 mice with placebo pellets developed more tumors than mice with estrogen pellets, 50% vs. 13%. GTG-obese mice with placebo pellets had a 100% tumor incidence compared to 50% and 20% for GTG-lean and controls without estrogen. Serum leptin was higher in obese compared to lean mice and adiponectin was not affected by body weight. Adiponectin:leptin ratio was significantly reduced in obese compared to lean mice. Leptin, leptin receptor and signaling protein expression were determined in mammary and tumor tissue. Leptin and STAT3 were most abundant in tumors. These findings suggest that in vivo estrogen suppressed proliferation of T47-D cells but without supplemental estrogen obesity enhanced tumor development. The exact reason for this is not presently clear.
Nkhata
Katai J
KJ
Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Ray
Amitabha
A
Dogan
Soner
S
Grande
Joseph P
JP
Cleary
Margot P
MP
D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D020738:Leptin / Q000097:blood; D051379:Mice; D008819:Mice, Nude; D008820:Mice, Obese; D009368:Neoplasm Transplantation; D010052:Ovariectomy; D011960:Receptors, Estrogen
D004967:Estrogens; D020738:Leptin; D011960:Receptors, Estrogen; D004958:Estradiol