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Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones

Diabetes Branch (S.Y., P.P., H.S., H.Z., L.S., B.S., J.E.-P., D.L.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and Nutrition and Molecular Carcinogenesis Section (N.P.N., N.C.P.S., S.N.P., J.C.B., S.D.H.), Laboratory of Biosystems and Cancer, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Medicine and Surgery (P.B., L.F.), McGill University Health Center, Royal Victoria Hospital, Montreal, Quebec, Canada H3A 1A1; Basic Research Program (N.C.P.S.), Science Applications International Corp.-Frederick, Inc., National Cancer Institute Frederick, Frederick, Maryland 21702-1201; and Department of Carcinogenesis (R.F.-Y., S.D.H.), University of Texas-M.D. Anderson Cancer Center, Smithville, Texas 78957

Address all correspondence and requests for reprints to: Shoshana Yakar, Ph.D., Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029-6574. E-mail: shoshana.yakar{at}mssm.edu.

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

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