Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-alpha mice.
BACKGROUND
Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-alpha 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-alpha 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.


CONCLUSIONS
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.
Dogan
Soner
S
Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Hu
Xin
X
Zhang
Yan
Y
Maihle
Nita J
NJ
Grande
Joseph P
JP
Cleary
Margot P
MP
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001835:Body Weight; D003720:Densitometry; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009765:Obesity / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D004041:Dietary Fats; D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D016211:Transforming Growth Factor alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2