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

Experimental Biology and Medicine - Tập 229 Số 2 - Trang 182-193 - 2004
Margot P. Cleary1, Subhash C. Juneja2, F. C. Phillips1, Xin Hu1, Joseph P. Grande3, Nita J. Maihle3
1Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, Minnesota, 55912
2Departments of Laboratory Medicine and Pathology
3Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905

Tóm tắt

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 104 weeks. Body weights of MMTV-TGF-α/Leprdb Leprdb mice were significantly heavier than those of the lean groups. No mammary tumors were detected in MMTV-TGF-α/LeprdbLeprdb mice, whereas the incidence of mammary tumors in MMTV-TGF-α/Lepr+ Lepr+ and MMTV-TGF-α/Lepr+ Leprdb mice was 69% and 82%, respectively. Examination of mammary tissue whole mounts indicated an absence of duct formation and branching for MMTV-TGF-α/Leprdb Leprdb mice. Both age at mammary tumor detection and tumor burden (tumors/mouse and tumor weights) were similar for the lean genotypes. Serum leptin levels of MMTV-TGF-α/Leprdb Leprdb mice were 12-20-fold higher than levels of lean mice. Thus, despite elevated serum leptin levels, leptin receptor-deficient MMTV-TGF-α/Leprdb Leprdb mice do not develop mammary tumors. This study provides additional evidence that leptin and its cognate receptor may be involved in mammary tumorigenesis.

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Experimental Biology and Medicine

Tập 229 Số 2

182-193

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