Hursting, Stephen D.

Hursting, Stephen D., Ph.D., M.P.H.

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Research Interests

Diet-gene interactions relevant to cancer prevention, particularly the molecular and hormonal mechanisms underlying energy balance-cancer associations

Current Research

1. Mechanism-Based Nutrition and Cancer Prevention Studies in Genetically Engineered Mice
Our work has focused on developing and using genetically altered mouse models to identify preventive, particularly nutritional, approaches to offset the increased cancer risk due to a genetic lesion such as loss of p53 or APC tumor suppressor activity or overexpression of growth signaling molecules including Wnt-1 and insulin-like growth factor-1 (IGF-1). We have reported that calorie restriction (CR) in p53-null (-/-) mice, Apc min, and Wnt-1 transgenic mice prevents adult-onset obesity, increases the latency of spontaneous tumor development, and decreases serum IGF-1 and leptin levels. In contrast, diet-induced obesity in these model systems enhances tumor development and increase levels of IGF-1 and leptin, as well as markers of insulin resistance and inflammation. Using diabetic A-Zip/F1 transgenic mice, which lack white adipose tissue but display insulin resistance, inflammation and increased tumor susceptibility, we are working to dissociate the relative roles of adiposity, insulin/IGF-1/leptin (and their associated signaling pathways) and inflammatory factors (including adipokines and cytokines). We have also begun to assess bioactive food components that target aspects of the insulin/IGF-1 signaling pathway and inflammatory pathways, as cancer prevention strategies in our tumor models.

2. Mechanisms Underlying the Energy Balance and Carcinogenesis Relationship: The Role of the IGF-1/Akt/mTOR Pathway
Obesity is an important risk factor for several human cancers, and the prevention of obesity by CR, physical activity, and related interventions in animal models suppresses tumor development and extends lifespan. We are currently testing the hypothesis that the anticancer and antiaging effects of CR and exercise are mediated by reduced levels of IGF-1/insulin resistance and inflammation. Using oligonucleotide microarrays, kinase arrays and other molecular approaches, we are evaluating the molecular changes in adipose tissue, epithelial target tissues and tumors in response to CR and exercise with and without modulation of IGF-1, insulin resistance and or inflammatory responses. In addition, we are comparing other energy balance-modulating interventions, such as diet-induced obesity and phytochemicals, to determine the key pathways linking energy balance and carcinogenesis.

3. Translational Nutrition and Chemoprevention Studies
In collaboration with colleagues in the Laboratory of Tumor Immunology and Biology at the NCI, and the San Antonio Cancer Institute, we are testing the hypothesis that dietary or chemopreventive interventions such as CR, exercise, phytonutrients, or specific inhibitors of the cyclooxygenase and Akt/mTOR pathways can be used in combination with cancer vaccines to enhance the immune response and reduce tumorigenesis relative to the vaccine or the nutritional regimen alone. We are also collaborating with colleagues in the Department of Epidemiology at MD Anderson and the San Antonio Cancer Institute to evaluate the pre-clinical effects of breast cancer chemopreventive agents including tamoxifen, raloxifene and aromatase inhibitors in combination with dietary or physical activity interventions.

Selected Publications

  1. Hursting SD, Nunez NP, Varticovski L, Vinson C. The obesity-cancer link: lessons learned from a fatless mouse, Cancer Res, 67 (6), 2391-3, 2007
  2. Takahashi Y, Perkins SN, Hursting SD, Wang TT. 17beta-Estradiol differentially regulates androgen-responsive genes through estrogen receptor-beta- and extracellular-signal regulated kinase-dependent pathways in LNCaP human prostate cancer cells, Mol Carcinog, 46 (2), 117-29, 2007
  3. Yakar S, Nunez NP, Pennisi P, Brodt P, Sun H, Fallavollita L, Zhao H, Scavo L, Novosyadlyy R, Kurshan N, Stannard B, East-Palmer J, Smith NC, Perkins SN, Fuchs-Young R, Barrett JC, Hursting SD, Leroith D. Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones, Endocrinology, 147 (12), 5826-34, 2006
  4. Fenton JI, Hursting SD, Perkins SN, Hord NG. Leptin induces an Apc genotype-associated colon epithelial cell chemokine production pattern associated with macrophage chemotaxis and activation, Carcinogenesis, 28 (2), 455-64, 2007
  5. Nunez NP, Oh WJ, Rozenberg J, Perella C, Anver M, Barrett JC, Perkins SN, Berrigan D, Moitra J, Varticovski L, Hursting SD, Vinson C. Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation, Cancer Res, 66 (10), 5469-76, 2006
  6. Colbert LH, Mai V, Tooze JA, Perkins SN, Berrigan D, Hursting SD. Negative energy balance induced by voluntary wheel running inhibits polyp development in APCMin mice, Carcinogenesis, 27 (10), 2103-7, 2006
  7. Fenton JI, Hursting SD, Perkins SN, Hord NG. Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line, Carcinogenesis, 27 (7), 1507-15, 2006
  8. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6, Cell, 124 (2), 315-29, 2006
  9. Fenton JI, Hord NG, Lavigne JA, Perkins SN, Hursting SD. Leptin, insulin-like growth factor-1, and insulin-like growth factor-2 are mitogens in ApcMin/+ but not Apc+/+ colonic epithelial cell lines, Cancer Epidemiol Biomarkers Prev, 14 (7), 1646-52, 2005
  10. Berrigan D, Lavigne JA, Perkins SN, Nagy TR, Barrett JC, Hursting SD. Phenotypic effects of calorie restriction and insulin-like growth factor-1 treatment on body composition and bone mineral density of C57BL/6 mice: implications for cancer prevention, In Vivo, 19 (4), 667-74, 2005

Contact Information


Mailing Address: Division of Nutritional Sciences
University of Texas at Austin
1 University Station, A2700
Austin, TX 78712
Physical Address: Experimental Sciences Building, Lab 324
Phone: 512-471-2809