Leptin Receptor-Deficient MMTV-TGF-α/LeprdbLepr db Female Mice Do Not Develop Oncogene-Induced Mammary Tumors

Being overweight is a risk factor for postmenopausal breast cancer and is associated with an increased incidence and shortened latency of spontaneous and chemically Induced mammary tumors in rodents. However, leptin-deficient obese Lepob Lepob female mice have reduced incidences of spontaneous and oncogene-induced mammary tumors. Of interest, leptin enhances the proliferation of human breast cancer cell lines in which leptin receptors are expressed, which suggests that leptin signaling plays a role in tumor development. We evaluated oncogene-induced mammary tumor development in obese MMTV-TGF-α/Leprdb Leprdb mice that exhibit a defect in OB-Rb, which is considered to be the major signaling isoform of the leptin receptor. Lepr and MMTV-TGF-α mice were crossed, and the offspring were genotyped for oncogene expression and the determination of Lepr status. Lean MMTV-TGF-α/Lepr+ Lepr+ (homozygous) and MMTV-TGF-α/Lepr+ Leprdb (heterozygous) mice and obese MMTV-TGF-α/Leprdb Leprdb mice were monitored until age 1...