Central Leptin Gene Therapy to Reduce Breast Cancer Risk Factors

摘要

Obesity is a risk factor for breast cancer, especially in postmenopausal women. Explanations for this association include increased production of estrogenic compounds due to aromatization of androgens to estrone in adipose tissue, and increased production of serum hormones/cytokines identified as promoters of breast tumor formation and growth. The long-term goal of the proposed research is to determine if control of obesity through centrally administered, recombinant adeno-associated virus leptin gene (rAAV- lep) therapy will decrease the incidence of mammary tumor formation, progression, or metastasis in the rat model. Leptin functions as a messenger in a feedback loop between adipose tissue and the hypothalamus and contributes to the regulation of energy intake, energy expenditure, and adaptation to starvation. The objective of this research was to determine whether central rAAV-lep gene therapy will cause a decrease in serum levels of positive risk factors for breast cancer. The results show that central leptin gene therapy is effective in preventing age-related weight gain in adult rats. We also show that the gene therapy is effective in decreasing circulating levels of several breast cancer risk factors, including leptin, insulin, and IGF-I. The results indicate that increasing hypothalamic leptin to control weight has the added benefit of reducing breast cancer risk factors.