Potential Role of Leptin Signaling in DMBA induced Mammary Tumors by Non-Responsive C57BL/6J Mice Fed a High-Fat DietGillespie C1, Quarshie A2, Penichet M3 and Gonzalez-Perez RR1*
- *Corresponding Author:
- Gonzalez-Perez Ruben R
Department of Microbiology, Biochemistry & Immunology
Morehouse School of Medicine, Atlanta, GA 30310, USA
E-mail: [email protected]
Received date: October 15, 2012; Accepted date: November 14, 2012; Published date: November 22, 2012
Citation: Gillespie C, Quarshie A, Penichet M, Gonzalez-Perez RR (2012) Potential Role of Leptin Signaling in DMBA-induced Mammary Tumors by Non- Responsive C57BL/6J Mice Fed a High-Fat Diet. J Carcinogene Mutagene 3:132. doi: 10.4172/2157-2518.1000132
Copyright: © 2012 Gillespie C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Environmental carcinogens, High-Fat Diet (HFD) and elevated levels of leptin correlate to increase breast cancer incidence. To test whether these factors could affect the development of Mammary Tumors (MT) via DMBA (7,12-dimethylbenz[a]anthracene) challenge, we used C57BL/6J mice that are non-responsive to develop MT in absence of hormonal stimulation. C57BL/6J female mice without hormonal stimulation were fed HFD (55% Kcalfat) and low-fat diets (10% Kcal-fat) received DMBA (oral gavage: 1 mg/weekly) for 6 weeks. To test whether leptin signaling is involved in DMBA-MT development, a potent inhibitor, pegylated leptin peptide receptor antagonist (PEG-LPrA2; half-life 66 hours), was used for 30 weeks. As expected, irrespective of PEG-LPrA2 treatment, lean mice fed with low-fat diet did not develop MT. However, HFD induced obesity and significantly stimulated earlier onset (within 18 weeks) and marginally increased the incidence of MT (21%; 3/14) in DIO-mice (diet-induced-obesity). It appears that leptin signaling may be involved in DMBA-induced mammary carcinogenesis in obese mice because no evidence of MT was found in DIO-mice treated with PEG-LPrA2 (0% incidence; 0/14; Wilcoxon-Breslow test Chi2, p=0.03). Interestingly, PEG-LPrA2 treatment did not apparently affect body weight or food intake, but reduced protein levels of several molecules related to breast cancer [Aryl hydrocarbon Receptor (AhR), leptin receptor (OBR), interleukin 1 receptor type I (IL-1R tI), hypoxia-induced factor 1 alpha (HIF-1α), Jagged1 (JAG1) and Notch1 activated (NICD1)] within the mammary glands. Our findings reinforce the idea that obesity induced by HFD is an additional risk factor for chemical-induced breast carcinogenesis. The present study reveals some potential mechanisms involving leptin in the effects of HFD and adiposity on mammary chemical-induced carcinogenesis. Overall, present data suggest that the inhibition of leptin signaling might be a new way to prevent breast cancer induced by chemical carcinogens, especially in obese individuals.