Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue

Rao, Ghanta N.; Ney, Elizabeth; Herbert, Ronald A.

doi:10.1023/a:1005822318256

Cited by 23 publications

(11 citation statements)

References 21 publications

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“…The NTP-2000 diet has been selected for the National Toxicology Program’s toxicology and carcinogenesis studies since 1995 (Rao et al, 1997). Soybean and fish meals are the major sources of protein, corn and wheat products are the major sources of carbohydrates, soy oil and corn oil are the major sources of fat, and alfalfa meal, oat hulls and purified cellulose are the major sources of fiber in this diet.…”

Section: Discussionmentioning

confidence: 99%

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Guo

Wang

Xiong

et al. 2014

Toxicology and Applied Pharmacology

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Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes.

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Section: Discussionmentioning

confidence: 99%

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Guo

Wang

Xiong

et al. 2014

Toxicology and Applied Pharmacology

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“…Transgenic founders were maintained, when not breeding, on the AIN 76A-Teklad-purified diet, with casein for protein, cornstarch and sucrose for carbohydrates, corn oil for fat, and purified cellulose for fiber, a diet shown to enhance mammary tumor formation in a previously published study (21).…”

Section: Methodsmentioning

confidence: 99%

HER2-Targeted Therapy Reduces Incidence and Progression of Midlife Mammary Tumors in Female Murine Mammary Tumor Virus huHER2-Transgenic Mice

Finkle¹,

Quan²,

Asghari³

et al. 2004

Clinical Cancer Research

112

139

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Purpose: This study examined the effectiveness of early and prolonged mu4D5 (the murine form of trastuzumab/ Herceptin) treatment in transgenic mice that overexpress human HER2 (huHER2), under the murine mammary tumor virus promoter, as a model of huHER2-overexpressing breast cancer.Experimental Design: Mice were randomly assigned to one of three treatment groups and received i.p. injections from 17 weeks of age until either 52 weeks of age or morbidity. Fourteen mice received 100 mg/kg mu4D5, 14 mice received 100 mg/kg antiherpes simplex virus glycoprotein D control antibody, and 11 mice received a diluent control.Results: High levels of huHER2 expression were detectable in mammary glands of young virgin founder mice. Mammary adenocarcinomas were frequently found in female founders and progeny at an average age of 28 weeks, with some progressing to metastatic disease. The incidence of mammary tumors was significantly reduced, and tumor growth inhibition was observed in mice receiving mu4D5 compared with control mice. In addition, Harderian gland neoplasms, highly associated with overexpression of hu-HER2 in this transgenic line, were entirely absent in the mu4D5 treatment group, indicating down-regulation of hu-HER2 in vivo activity.Conclusions: Early intervention with mu4D5 was of benefit in our transgenic mice at high risk for developing huHER2-overexpressing breast cancer. This study suggests a potential benefit of early treatment with Herceptin in HER2-positive primary breast cancer.

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“…The studies reported that the exposure reduced (Rao et al, 1997;Liu et al, 2005), increased (Thomsen et al, 2006), or had no effect (Day et al, 2001;Jin and MacDonald, 2002;Luijten et al, 2004) on mammary tumour incidence and/or multiplicity and size. In addition, a delayed tumour onset after genistein or soy exposure was reported in two of the six genetically modified mouse studies (Jin and MacDonald, 2002;Yang et al, 2003).…”

Section: Micementioning

confidence: 99%

The role of early life genistein exposures in modifying breast cancer risk

et al. 2008

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Review of the existing literature suggests that consumption of soy foods or an exposure to a soy isoflavone genistein during childhood and adolescence in women, and before puberty onset in animals, reduces later mammary cancer risk. In animal studies, an exposure that is limited to the fetal period or adult life does not appear to have the same protective effect. A meta-analysis of human studies indicates a modest reduction in pre-and postmenopausal risk when dietary intakes are assessed during adult life. These findings concur with emerging evidence indicating that timing may be vitally important in determining the effects of various dietary exposures on the susceptibility to develop breast cancer. In this review, we address the mechanisms that might mediate the effects of an early life exposure to genistein on the mammary gland. The focus is on changes in gene expression, such as those involving BRCA1 and PTEN. It will be debated whether mammary stem cells are the targets of genistein-induced alterations and also whether the alterations are epigenetic. We propose that the effects on mammary gland morphology and signalling pathways induced by pubertal exposure to genistein mimic those induced by the oestrogenic environment of early first pregnancy.

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Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue

Cited by 23 publications

References 21 publications

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

HER2-Targeted Therapy Reduces Incidence and Progression of Midlife Mammary Tumors in Female Murine Mammary Tumor Virus huHER2-Transgenic Mice

The role of early life genistein exposures in modifying breast cancer risk

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