Breast cancer is the most common cancer in women. Visceral obesity and body weight gain are associated with the increased risk of postmenopausal breast cancer. Adiponectin is an adipokine possessing anti-tumor activities against various types of obesity-related cancers. The present study has established a MMTV-polyomavirus middle T antigen (PyVT) transgenic mouse deficient with adiponectin (ADN) expression. Compared to the control mice [PyVT(+/−)ADN(+/+)], the development of mammary tumors in mice lacking this adipokine [PyVT(+/−)ADN(-/-)] was significantly accelerated. While the serum total cholesterol was progressively decreased from week 11 onwards, the cholesterol content in tumor tissues was elevated in both types of mice. The ratio between serum LDL-cholesterol and HDL-cholesterol was significantly higher in PyVT(+/−)ADN(-/-) mice than that in PyVT(+/−)ADN(+/+) mice. Adiponectin was able to inhibit cholesterol uptake in both MDA-MB-231 human breast cancer cells and the primary tumor cells isolated from PyVT transgenic mice. These data demonstrated that the anti-breast cancer activity of adiponectin was at least in part attributed to its suppressive effects on cholesterol accumulation in mammary tumors.
This work is supported by Research Grants Council of Hong Kong (Project no.777908M). Adiponectin knockout mice were kindly provided by Dr. Lawrence Chan at Baylor College of Medicine, who generated these mice with the support of the US National Institutes of Health grant HL-51586.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-03-07.