Research article

Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice

Soner Dogan¹ , Xin Hu¹ , Yan Zhang² , Nita J Maihle³ , Joseph P Grande⁴ and Margot P Cleary¹

¹  Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA

²  Biostatistics Core, University of Minnesota Cancer Center, B484-4 Mayo, 420 Delaware Street SE, Minneapolis, MN 55455, USA

³  Department of Obstetrics and Gynecology, Yale University Medical School, 300 George Street, Suite 8100, New Haven, CT 06511, USA

⁴  Department of Pathology and Laboratory Medicine, Mayo Foundation, 200 Second Street SW, Rochester, MN 55905, USA

author email corresponding author email

Breast Cancer Research 2007, 9:R91doi:10.1186/bcr1840

Published:	27 December 2007

Abstract

Introduction

Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-α mice with dietary-induced obesity. One link between obesity and breast cancer is the adipokine, leptin. Here, the focus is on diet-induced obesity and MT and mammary fat pad (MFP) leptin and apoptotic signaling proteins.

Methods

MMTV-TGF-α mice were fed low-fat or high-fat diets from 10 to 85 weeks of age. High-Fat mice were divided into Obesity-Prone and Obesity-Resistant groups based on final body weights. Mice were followed to assess MT development and obtain serum, MFP, and MT.

Results

Incidence of palpable MTs was significantly different: Obesity-Prone > Obesity-Resistant > Low-Fat. Serum leptin was significantly higher in Obesity-Prone compared with Obesity-Resistant and Low-Fat mice. Low-Fat mice had higher MFP and MT ObRb (leptin receptor) protein and Jak2 (Janus kinase 2) protein and mRNA levels in comparison with High-Fat mice regardless of body weight. Leptin (mRNA) and pSTAT3 (phosphorylated signal transducer and activator of transcription 3) (mRNA and protein) also were higher in MTs from Low-Fat versus High-Fat mice. Expression of MT and MFP pro-apoptotic proteins was higher in Low-Fat versus High-Fat mice.

Conclusion

These results confirm a connection between body weight and MT development and between body weight and serum leptin levels. However, diet impacts MT and MFP leptin and apoptosis signaling proteins independently of body weight.