TY - JOUR
T1 - Effects of intermittent and chronic calorie restriction on mammalian target of rapamycin (mTOR) and IGF-I signaling pathways in mammary fat pad tissues and mammary tumors
AU - Dogan, Soner
AU - Johannsen, Anna C.
AU - Grande, Joseph P.
AU - Cleary, Margot P.
N1 - Funding Information:
This work was supported by grants CA101858 (MPC), DK16105 (JPG), and the Breast Cancer Research Foundation and the Hormel Foundation. We thank Dr. Michael E. Gross-mann for helpful suggestions in revising the manuscript. We also acknowledge the assistance of Dr. Olga P. Rogozina and Ms. Melissa J. L. Bonorden in overseeing the breeding and genotyping protocols to obtain the experimental animals.
PY - 2011/4
Y1 - 2011/4
N2 - Chronic calorie restriction (CCR) prevents mammary tumor (MT) development in rodents. We reported that intermittent calorie restriction (ICR) provides greater protection than CCR in MMTV-TGF-α mice. The mammalian target of rapamycin (mTOR) pathway is involved in MT development. Here the impact of ICR versus CCR on proteins associated with mTOR signaling in mammary tissues and MTs from MMTV-TGF-α mice was determined. Mice were enrolled at 10 wk of age into ad libitum-fed (AL), CCR, and ICR groups and followed until 37/38 or 73/74 wk of age. Time points 37 and 73 followed 3 wk of 50% restriction for ICR mice, while 38 and 74 followed 1 wk of refeeding of ICR mice. Calorie restriction reduced serum IGF-I levels except for older CCR mice. At 37/38 wk, calorie restriction decreased mTOR, p70S6K, HIF-1, EGFR, and Erk protein activation and increased p4EBP1 and VEGF in mammary fat pads. At 73/74 wk, both modes of calorie restriction lowered IGF-I protein expression levels and Akt activation in MTs and mammary fat pads, and CCR increased mTOR, p70S6K, p4EBP1, and HIF-1 expression. ICR had inconsistent effects on these proteins in older mice. These results indicate that mTOR signaling proteins are modulated by age and type of calorie restriction.
AB - Chronic calorie restriction (CCR) prevents mammary tumor (MT) development in rodents. We reported that intermittent calorie restriction (ICR) provides greater protection than CCR in MMTV-TGF-α mice. The mammalian target of rapamycin (mTOR) pathway is involved in MT development. Here the impact of ICR versus CCR on proteins associated with mTOR signaling in mammary tissues and MTs from MMTV-TGF-α mice was determined. Mice were enrolled at 10 wk of age into ad libitum-fed (AL), CCR, and ICR groups and followed until 37/38 or 73/74 wk of age. Time points 37 and 73 followed 3 wk of 50% restriction for ICR mice, while 38 and 74 followed 1 wk of refeeding of ICR mice. Calorie restriction reduced serum IGF-I levels except for older CCR mice. At 37/38 wk, calorie restriction decreased mTOR, p70S6K, HIF-1, EGFR, and Erk protein activation and increased p4EBP1 and VEGF in mammary fat pads. At 73/74 wk, both modes of calorie restriction lowered IGF-I protein expression levels and Akt activation in MTs and mammary fat pads, and CCR increased mTOR, p70S6K, p4EBP1, and HIF-1 expression. ICR had inconsistent effects on these proteins in older mice. These results indicate that mTOR signaling proteins are modulated by age and type of calorie restriction.
UR - http://www.scopus.com/inward/record.url?scp=79957568029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957568029&partnerID=8YFLogxK
U2 - 10.1080/01635581.2011.535968
DO - 10.1080/01635581.2011.535968
M3 - Article
C2 - 21462085
AN - SCOPUS:79957568029
SN - 0163-5581
VL - 63
SP - 389
EP - 401
JO - Nutrition and Cancer
JF - Nutrition and Cancer
IS - 3
ER -