Leptin Regulation of Mammary Tumorigenesis

Abstract : Recently it was shown that many breast cancer cell lines express leptin. In addition, leptin is increased in the plasma and adipose tissue of women with breast cancer. To investigate the role of leptin in mammary tumorigenesis, we asked whether estrogen regulated leptin expression, when during tumorigenesis leptin was first expressed, and developed tools to examine the functional consequences of leptin expression in mammary tissue. We examined leptin mRNA levels in numerous breast cancer cell lines and human tumors, confirming that leptin is widely expressed in this epithelium. There was no correlation between level of leptin expression and the mRNA levels for ER alpha or beta. Furthermore, in normal human organoids and in NcF7 cells, estrogen did not regulate the level of leptin expression. Neither DMBA-induced rat mammary tumors nor normal epithelium from DMBA treated or control rats showed any expression of leptin by RT-PCR, whereas leptin in rat mammary adipose tissue was abundant. Finally, we cloned the full-length human leptin cDNA into pcDNA3.lD/V5-His-TOPO (Invitrogen) and are making stably transfected clones for additional studies on the role of leptin in mammary tumorigenesis.