High levels of dietary soy decrease mammary tumor latency and increase incidence in MTB-IGFIR transgenic mice

Watson, Katrina L.; Stalker, Leanne; Jones, Robert A.; Moorehead, Roger A.

doi:10.1186/s12885-015-1037-z

Cited by 10 publications

(9 citation statements)

References 75 publications

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“…Primer efficiencies were as follows, Spp1 – 104, Itgav – 101, Itgb3 – 99, Cd44 – 101, Hprt – 105, and Ywhaz – 110. The expression of Spp1, Itgav, Itgb3 and Cd44 were determined relative to the house-keeping genes Hprt and Ywhaz which were previously been shown to be suitable from a panel of 14 potential housekeeping genes [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

et al. 2016

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BackgroundOsteopontin is a secreted phosphoglycoprotein that is expressed by a number of normal cells as well as a variety of tumor cells. With respect to breast cancer, osteopontin has been implicated in regulating tumor cell proliferation and migration/metastasis and may serve as a prognostic indicator. However it remains unclear whether osteopontin has the same impact in all breast cancer subtypes and in particular, osteopontin’s effects in claudin-low breast cancer are poorly understood.MethodscDNA microarrays and qRT-PCR were used to evaluate osteopontin expression in mammary tumors from MTB-IGFIR transgenic mice and cell lines derived from these tumors. siRNA was then used to determine the impact of osteopontin knockdown on proliferation, apoptosis and migration in vitro in two murine claudin-low cell lines as well as identify the receptor mediating osteopontin’s physiologic effects.ResultsOsteopontin was expressed at high levels in mammary tumors derived from MTB-IGFIR transgenic mice compared to normal mammary tissue. Evaluation of cell lines derived from different mammary tumors revealed that mammary tumor cells with claudin-low characteristic expressed high levels of osteopontin whereas mammary tumor cells with mixed luminal and basal-like features expressed lower levels of osteopontin. Reduction of osteopontin levels using siRNA significantly reduced proliferation and migration while increasing apoptosis in the claudin-low cell lines. Osteopontin’s effect appear to be mediated through a receptor containing ITGAV and not through CD44.ConclusionsOur data suggests that mammary tumors with a mixed luminal/basal-like phenotype express high levels of osteopontin however this osteopontin appears to be largely produced by non-tumor cells in the tumor microenvironment. In contrast tumor cells with claudin-low characteristics express high levels of osteopontin and a reduction of osteopontin in these cells impaired proliferation, survival and migration.

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Section: Methodsmentioning

confidence: 99%

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

et al. 2016

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“…[100] Soy containing various concentrations of isoflavones when fed at high levels to MTB-IGFIR transgenic mice (mice developing mammary tumours by the over expression of type I insulin-like growth factor receptor) promoted the development of mammary tumors which appears to be associated with increased expression of Areg (marker of ER signaling). [101] A meta-analysis study by Hamilton-Reeves et al, [102] suggested that neither soy foods nor its isoflavones have any significant impact on the reproductive hormone (testosterone) levels in men with the risk of prostate cancer (PC). A 6month intervention of mixed SI had no effect in reducing breast epithelial proliferation in healthy, high risk adult western women (n = 126).…”

mentioning

confidence: 99%

Soy Bioactive Components in Functional Perspective: A Review

Garg

Lule

Malik

et al. 2016

International Journal of Food Properties

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Functional foods are the focus of attraction for well-being. The healthy living of Asians may be attributed to a diet enriched with soy isoflavones viz. genistein and daidzein which fills the gap of proteinaceous diet in vegetarians. Several factors, such as administration, dosage, metabolism, ingestion of other pharmacological substances, type of estrogen receptors, and presence or absence of endogenous estrogen, affect the activities and bioavailability of isoflavones. The mode of therapeutic action could be either through the stimulation of estrogen receptors or by the non-involvement of estrogen receptors. Soy, due to its isoflavones content, serves as a balanced and remedial substitute in combating various lifestyle disorders, like cancer prevention, by interruption of the breakdown of extracellular matrix that surrounds growing vessels and tumors, lowering of lipid and blood insulin levels by regulating lipid and glucose metabolism, alleviation of menopausal symptoms, and osteoprotective effects by modulating estrogen receptors, thus acting as a safer switch to hormone replacement therapy, anti-hypertensive effect which may also contribute to cardioprotective, anti-oxidative effect, regulation of cognitive functions, and many others. Therefore, it could be regarded as a valuable therapeutics. However, since soy isoflavones also act as endocrine disruptors, they also possess some negative effects. Concerns have been raised in relation to thyroid function abnormality. In view of the previously mentioned facts an attempt has been made to review the literature available on both beneficial as well as deleterious role of isoflavones, soy derived bioactive compounds.

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“…In addition to the transgenic mice describe above, MTB-IGFIR transgenic mice [65] have also been used to investigate soy isoflavone’s impact on mammary tumorigenesis [66]. MTB-IGFIR transgenic mice overexpress the human insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells in a doxycycline-inducible manner [65].…”

Section: Rodent Mammary Tumor Modelsmentioning

confidence: 99%

“…Meanwhile, the other study found no impact on tumor incidence in MMTV- neu transgenic mice fed a high soy diet compared to controls [95]. In the study using MTB-IGFIR mice, tumor incidence was increased and tumor latency was decreased in MTB-IGFIR mice fed a diet containing 20% ISP compared to casein-fed MTB-IGFIR mice [66].…”

Section: Mammary Tumor Development Following Lifetime Soy Isoflavomentioning

confidence: 99%

Rodent Models Assessing Mammary Tumor Prevention by Soy or Soy Isoflavones

Moorehead

2019

Genes

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While epidemiological studies performed in Asian countries generally show that high levels of dietary soy are associated with reduced breast cancer risk, studies in Western countries have typically failed to show this correlation. In an attempt to model the preventative actions of soy on mammary tumor development, rodent models have been employed. Thirty-four studies were identified that evaluated the impact of soy products or purified soy isoflavones on mammary tumor initiation (studies evaluating established mammary tumors or mammary tumor cell lines were not included) and these studies were separated into mammary tumors induced by chemical carcinogens or transgenic expression of oncogenes based on the timing of soy administration. Regardless of when soy-based diets or purified isoflavones were administered, no consistent protective effects were observed in either carcinogen-induced or oncogene-induced mammary tumors. While some studies demonstrated that soy or purified isoflavones could reduce mammary tumor incidence, other studies showed either no effect or tumor promoting effects of soy products or isoflavones. Most importantly, only five studies found a decrease in mammary tumor incidence and six studies observed a decrease in tumor multiplicity, two relevant measures of the tumor preventative effects of soy or isoflavones. The variable outcomes of the studies examined were not completely surprising given that few studies employed the same experimental design. Future studies should be carefully designed to more accurately emulate soy consumption observed in Asian cultures including lifetime exposure to less refined soy products and potentially the incorporation of multigenerational feeding studies.

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High levels of dietary soy decrease mammary tumor latency and increase incidence in MTB-IGFIR transgenic mice

Cited by 10 publications

References 75 publications

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

Soy Bioactive Components in Functional Perspective: A Review

Rodent Models Assessing Mammary Tumor Prevention by Soy or Soy Isoflavones

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