title: Ovariectomy is associated with metabolic impairments and enhanced mammary tumor growth in MKR mice.
abstract: Obesity and type 2 diabetes (T2D) are associated with an increased risk of breast cancer incidence and mortality. Common features of obesity and T2D are insulin resistance and hyperinsulinemia. A mammary tumor promoting effect of insulin resistance and hyperinsulinemia was demonstrated in the transgenic female MKR mouse model of pre-diabetes inoculated with mammary cancer cells. Interestingly, in MKR mice, as well as in other diabetic mouse models, males exhibit severe hyperglycemia, while females display insulin resistance and hyperinsulinemia with only a mild increase in blood glucose levels. This gender-specific protection from hyperglycemia may be attributed to estradiol, a key player in the regulation of the metabolic state, including obesity, glucose homeostasis, insulin resistance, and lipid profile. The aim of this study was to investigate the effects of ovariectomy (including the removal of endogenous estradiol) on the metabolic state of MKR female mice and subsequently on the growth of Mvt-1 mammary cancer cells, inoculated into the mammary fat pad of ovariectomized mice, compared with sham-operated mice. The results showed an increase in body weight, accompanied by increased fat mass, elevated blood glucose levels, and hypercholesterolemia, in ovariectomized MKR mice. In addition, mammary tumor growth was significantly higher in these mice. The results suggest that ovarian hormone deficiency may promote impaired metabolic homeostasis in the hyperinsulinemic MKR female mice, which in turn is associated with an increased growth of mammary tumors.
authors.affiliation: Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Reseasch Institute at Rambam (CRIR), Rambam Medical Center, P.O.B 9602, Haifa 31096, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Ben-Shmuel
authors.affiliation: Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Reseasch Institute at Rambam (CRIR), Rambam Medical Center, P.O.B 9602, Haifa 31096, Israel.
authors.forename: Eyal J
authors.initials: EJ
authors.lastname: Scheinman
authors.affiliation: Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Reseasch Institute at Rambam (CRIR), Rambam Medical Center, P.O.B 9602, Haifa 31096, Israel.
authors.forename: Rola
authors.initials: R
authors.lastname: Rashed
authors.affiliation: Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Reseasch Institute at Rambam (CRIR), Rambam Medical Center, P.O.B 9602, Haifa 31096, Israel.
authors.forename: Zila Shen
authors.initials: ZS
authors.lastname: Orr
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1055, Atran 4-36, New York, NY 10029, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gallagher
authors.affiliation: Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Reseasch Institute at Rambam (CRIR), Rambam Medical Center, P.O.B 9602, Haifa 31096, Israel.|Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1055, Atran 4-36, New York, NY 10029, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.affiliation: Diabetes and Metabolism Clinical Research Center of Excellence, Clinical Reseasch Institute at Rambam (CRIR), Rambam Medical Center, P.O.B 9602, Haifa 31096, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Rostoker
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D007333:Insulin Resistance; D008325:Mammary Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010052:Ovariectomy / Q000009:adverse effects*; D011236:Prediabetic State / Q000235:genetics / Q000473:pathology*
chemical_list: D001786:Blood Glucose
keywords: breast cancer; hyperinsulinemia; insulin resistance; obesity; ovariectomy