Weight control by exercise and dietary calorie restriction (DCR) has been associated with reduced cancer risk, but the underlying mechanisms are not well understood. This study was designed to compare the effects of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways. SENCAR mice were randomly assigned to one of the following five groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AL؉Exe), exercise but pair-fed at the amount as controls (PF؉Exe), 20% DCR, and 20% DCR plus exercise (DCR؉Exe). After 10 weeks, body weight and body fat significantly decreased in the groups of DCR, DCR؉Exe, and PF؉Exe when compared with the controls. AL؉Exe did not induce weight loss due to, at least in part, increased food intake. Plasma IGF-1 levels reduced significantly in DCR and DCR؉Exe but not PF؉Exe. The protein H-Ras and activated Ras-GTP significantly decreased in TPA-induced skin tissues of DCR-fed mice but not exercised mice. PI3K protein, phosphoserine Akt, and p42/p44-MAPK were reduced, however, in both DCR and PF؉Exe groups. Immunohistochemistry demonstrated that the significantly reduced H-Ras occurred in subcutaneous fat cells, while the reduced PI3K and PCNA took place only in the epidermis. Plasma leptin decreased in PF؉Exe, DCR, and DCR؉Exe, while the caspase-3 activity increased in DCR؉Exe only. Genomic microarray analysis further indicated that the expression of 34 genes relevant to PI3K and 31 genes to the MAPK pathway were significantly regulated by either DCR or PF؉Exe treatments. The reduced PI3K in PF؉Exe mice was partially reversed by IGF-1 treatment. The overall results of this study demonstrated that DCR abrogated both Ras and PI3K signaling, which might inhibit TPA-induced proliferation and anti-apoptosis. Selective inhibition of PI3K by PF؉Exe but not AL؉Exe seems more attributable to the magnitude of the caloric deficit and/or body fat loss than diet versus exercise comparison.The National Health and Nutrition Examination Survey indicates growing rates of obesity in American adults and overweight children over the past 20 years (1). Numerous prospective and case-control studies associated with weight control and physical activity estimate that excess body weight and sedentary life style account for about 39% endometrial, 25% kidney, 11% colon, 9% postmenopausal breast cancer, and 5% total cancer incidence (2-3). It has been suggested that those 25% over normal weight have a 33% greater cancer risk than those who maintain ideal body weight (4). Therefore, for many individuals, it would be advisable to maintain weight within the normal range to reduce their risk of cancer.Overweight/obesity is recognized as a reflection of a positive energy state that results from either over-consumption of energy or low energy expenditure. There is ample evidence that weight control via decreasing calorie intake and/or increasing physical activity reduces cancer risk in animal models. For almost a century, dietary calorie restr...

Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the effect of exercise with dietary consideration on the phospholipid profile in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control; ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL); and treadmill-exercised but pair-fed with the same amount as the control (Ex+PF). After 14 weeks, Ex+PF but not Ex+AL mice showed ∼25% decrease in both body weight and body fat when compared with the controls. Of the total 338 phospholipids determined by electrospray ionization-tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36% to 75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI 3-kinase in TPA-induced skin epidermis, as measured by both Western blotting and immunohistochemistry. In addition, ∼2-fold increase of the long-chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines was observed in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake, but not exercise alone, significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPAinduced PI 3-kinase and by enhancing ω-3 fatty acid elongation. Cancer Prev Res; 3(4); 466-77. ©2010 AACR.

NAC transcription factors are known to be involved in regulation of plant responses to drought stress. In this study, the expression of 23 drought-responsive GmNAC genes was assessed in the shoot tissues of DT51 and MTD720, the two soybean varieties with contrasting drought-responsive phenotypes, by real-time quantitative PCR (RT-qPCR) under normal and drought conditions. Results indicated that expression profile of GmNAC genes was genotype-dependent, and six GmNACs (GmNAC019, 043, 062, 085, 095 and 101) had higher transcript levels in the shoots of the drought-tolerant DT51 in comparison with the drought-sensitive MTD720 under drought. Our study suggests a positive correlation between the higher drought tolerance degree of DT51 versus MTD720 and the up-regulation of at least these six drought-responsive GmNACs in the shoot tissues. Furthermore, on the basis of our analysis, three genes, GmNAC043, 085 and 101, were identified as promising candidates for development of drought-tolerant soybean cultivars by genetic engineering.

Abiotic stress factors, such as drought and salinity, are known to negatively affect plant growth and development. To cope with these adverse conditions, plants have utilized certain defense mechanisms involved in various aspects, including morphological, biochemical and molecular alterations. Particularly, a great deal of evidence for the biological importance of the plant-specific NAM, ATAF1/2, CUC2 (NAC) transcription factors (TFs) in plant adaptation to abiotic stress conditions has been reported. A previous in planta study conducted by our research group demonstrated that soybean (Glycine max) GmNAC085 mediated drought resistance in transgenic Arabidopsis plants. In this study, further characterization of GmNAC085 function in association with salt stress was performed. The findings revealed that under this condition, transgenic soybean plants overexpressing GmNAC085 displayed better germination rates than wild-type plants. In addition, biochemical and transcriptional analyses showed that the transgenic plants acquired a better defense system against salinity-induced oxidative stress, with higher activities of antioxidant enzymes responsible for scavenging hydrogen peroxide or superoxide radicals. Higher transcript levels of several key stress-responsive genes involved in the proline biosynthetic pathway, sodium ion transporter and accumulation of dehydrins were also observed, indicating better osmoprotection and more efficient ion regulation capacity in the transgenic lines. Taken together, these findings and our previous report indicate that GmNAC085 may play a role as a positive regulator in plant adaptation to drought and salinity conditions.