Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones.
Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.
Nunez
Nomeli P
NP
Laboratory of Biosystems and Cancer, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1758, USA.
Perkins
Susan N
SN
Smith
Nicole C P
NC
Berrigan
David
D
Berendes
David M
DM
Varticovski
Lyuba
L
Barrett
J Carl
JC
Hursting
Stephen D
SD
D000818:Animals; D015992:Body Mass Index; D004195:Disease Models, Animal; D005260:Female; D006728:Hormones / Q000502:physiology; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000150:complications / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009765:Obesity / Q000150:complications* / Q000473:pathology; D010052:Ovariectomy; D017698:Postmenopause; D051155:Wnt1 Protein / Q000235:genetics
D006728:Hormones; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse