Reduced Mitogenicity of Sera Following Weight Loss in Premenopausal Women

We investigated whether serum from normal weight women is less mitogenic and more apoptotic than sera from the same women in the overweight state. Sera from premenopausal women, age (mean ± SEE) 34.6 ± 0.53 years, who were randomized to caloric restriction (CR) (n = 13), CR + aerobic exercise (AE) (n = 14), or CR + resistance training (RT) (n = 20) were used to culture endometrial cancer cells. Phases of the cell cycle were determined, and proliferating cell nuclear antigen (PCNA) positivity was used to assess proliferation and apoptosis was assessed by determining cleaved caspase-3 and poly-ADP-ribose polymerase (PARP). Analyses showed that overall, cells grown in sera from the weight-reduced state had significantly more cells in G0/G1 and significantly fewer cells in the S and G2/M phases of the cell cycle than cells grown in sera from the overweight state. PCNA staining confirmed that cells grown in sera from the weight-reduced state had fewer proliferating cells. Cleaved caspase-3 and PARP were not different in cells grown in sera from the weight-reduced state compared to the overweight state. We conclude that weight loss with or without exercise could lower the risk for cancer through changes in serum that result in reduced cellular mitogenicity.

[1]  Nidhal Ben Amor,et al.  TNF-α and its inhibitors in cancer , 2010, Medical oncology.

[2]  Y. DeClerck,et al.  Interleukin-6 in bone metastasis and cancer progression. , 2010, European journal of cancer.

[3]  G. Hunter,et al.  Exercise Training Prevents Regain of Visceral Fat for 1 Year Following Weight Loss , 2010, Obesity.

[4]  D. Berrigan,et al.  Distinct Effects of Calorie Restriction and Exercise on Mammary Gland Gene Expression in C57BL/6 Mice , 2009, Cancer Prevention Research.

[5]  S. Linn,et al.  Cancer incidence in Israeli Jewish survivors of World War II. , 2009, Journal of the National Cancer Institute.

[6]  Sterling C. Johnson,et al.  Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys , 2009, Science.

[7]  Weiqin Jiang,et al.  Effect of Nonmotorized Wheel Running on Mammary Carcinogenesis: Circulating Biomarkers, Cellular Processes, and Molecular Mechanisms in Rats , 2008, Cancer Epidemiology Biomarkers & Prevention.

[8]  M. Zwahlen,et al.  Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies , 2008, The Lancet.

[9]  Baofeng Yang,et al.  Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. , 2007, Endocrine-related cancer.

[10]  C. Ulrich,et al.  Effect of a 12-Month Exercise Intervention on the Apoptotic Regulating Proteins Bax and Bcl-2 in Colon Crypts: A Randomized Controlled Trial , 2007, Cancer Epidemiology Biomarkers & Prevention.

[11]  K. Courneya,et al.  Effects of Aerobic Exercise Training on Estrogen Metabolism in Premenopausal Women: A Randomized Controlled Trial , 2007, Cancer Epidemiology Biomarkers & Prevention.

[12]  D. Voskuil,et al.  Physical Activity and Endometrial Cancer Risk, a Systematic Review of Current Evidence , 2007, Cancer Epidemiology Biomarkers & Prevention.

[13]  D. Voskuil,et al.  Physical Activity and Breast Cancer: A Systematic Review , 2007, Epidemiology.

[14]  Aleksandr E. Vendrov,et al.  ECC-1 Cells: A Well-Differentiated Steroid-Responsive Endometrial Cell Line with Characteristics of Luminal Epithelium1 , 2006, Biology of reproduction.

[15]  J. Potter,et al.  Effect of a 12-Month Exercise Intervention on Patterns of Cellular Proliferation in Colonic Crypts: A Randomized Controlled Trial , 2006, Cancer Epidemiology Biomarkers & Prevention.

[16]  R. Barnard,et al.  Effects of a Low-Fat, High-Fiber Diet and Exercise Program on Breast Cancer Risk Factors In Vivo and Tumor Cell Growth and Apoptosis In Vitro , 2006, Nutrition and cancer.

[17]  F. Anania,et al.  Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. , 2006, Endocrine-related cancer.

[18]  C. Burger,et al.  Steroid-Modulated Proliferation of Human Endometrial Carcinoma Cell Lines: Any Role for Insulin-like Growth Factor Signaling? , 2005, The Journal of the Society for Gynecologic Investigation: JSGI.

[19]  Liqin Wang,et al.  Antiapoptotic effects of estrogen in normal and cancer human cervical epithelial cells. , 2004, Endocrinology.

[20]  D. Grobbee,et al.  Breast cancer risk after caloric restriction during the 1944-1945 Dutch famine. , 2004, Journal of the National Cancer Institute.

[21]  K. Michels,et al.  Caloric restriction and incidence of breast cancer. , 2004, JAMA.

[22]  S. Tretli,et al.  Lifestyle changes during adolescence and risk of breast cancer: an ecologic study of the effect of World War II in Norway , 1996, Cancer Causes & Control.

[23]  D. Nemet,et al.  Negative energy balance plays a major role in the IGF-I response to exercise training. , 2004, Journal of applied physiology.

[24]  A. Folsom,et al.  Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study , 2003, International Journal of Obesity.

[25]  W. Aronson,et al.  A low‐fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro , 2003, The Prostate.

[26]  W. Aronson,et al.  Insulin-like growth factor I (IGF-I) and IGF binding protein-1 modulate prostate cancer cell growth and apoptosis: possible mediators for the effects of diet and exercise on cancer cell survival. , 2003, Endocrinology.

[27]  Michael J Thun,et al.  Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. , 2003, The New England journal of medicine.

[28]  U. Das.  Is obesity an inflammatory condition? , 2001, Nutrition.

[29]  N. Auersperg,et al.  Estradiol up-regulates antiapoptotic Bcl-2 messenger ribonucleic acid and protein in tumorigenic ovarian surface epithelium cells. , 2001, Endocrinology.

[30]  D. Yee,et al.  The IGF system and breast cancer. , 2001, Endocrine-related cancer.

[31]  A. Porter,et al.  Emerging roles of caspase-3 in apoptosis , 1999, Cell Death and Differentiation.

[32]  D. Carpenter,et al.  Environmental pollution and child health in central and Eastern Europe. , 1998, Environmental health perspectives.

[33]  J. Davis,et al.  Exercise effects on lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[34]  D. Gaylor,et al.  Upregulation of apoptosis with dietary restriction: implications for carcinogenesis and aging. , 1998, Environmental health perspectives.

[35]  Simon C Watkins,et al.  Current Protocols In Cytometry , 1997 .

[36]  Z. Darżynkiewicz,et al.  Differential Staining of DNA and RNA , 1997 .

[37]  B. Macneil,et al.  Exercise training and tumour metastasis in mice: influence of time of exercise onset. , 1993, Anticancer research.

[38]  J. French,et al.  The growth hormone: insulin-like growth factor 1 axis is a mediator of diet restriction-induced inhibition of mononuclear cell leukemia in Fischer rats. , 1993, Cancer research.

[39]  A. Tannenbaum,et al.  The influence of the degree of caloric restriction on the formation of skin tumors and hepatomas in mice. , 1949, Cancer research.