Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone‐poor soy protein concentrate

Chiesa, Giulia; Rigamonti, Elena; Lovati, Maria Rosa; Disconzi, E.; Soldati, Sabina; Sacco, Maria Grazia; Catò, Enrica Mira; Patton, Veronica; Scanziani, Eugenio; Vezzoni, Paolo; Arnoldi, Anna; Locati, Daniela; Sirtori, Cesare R.

doi:10.1002/mnfr.200700296

Cited by 9 publications

(5 citation statements)

References 68 publications

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“…Bioactive components present in soy foods, specifically the soy isoflavone genistein (GEN) have been a focus of our studies given the many health benefits attributed to dietary soy intake (Dong and Qin 2011;Jin and MacDonald 2002;Chiesa et al 2008;Caan et al 2011;Shu et al 2009). These beneficial effects are considered to be particularly manifest in the lower risk of breast cancer reported for Asian women who consume soy-based foods as part of their regular diets beginning in early life (Korde et al 2009;Dong and Qin 2011).…”

Section: Introductionmentioning

confidence: 99%

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

Pabona

Dave

et al. 2012

Genes Nutr

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Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature and precise actions of specific bioactive components present in foods with purported health effects. The 43-amino acid peptide lunasin (LUN) is found in soybeans, is bioavailable similar to the isoflavone genistein (GEN), and thus may mediate the beneficial effects of soy food consumption. Here, we evaluated whether LUN displays common and distinct actions from those of GEN in non-malignant (mouse HC11) and malignant (human MCF-7) mammary epithelial cells. In MCF-7 cells, LUN up-regulated tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN) promoter activity, increased PTEN transcript and protein levels and enhanced nuclear PTEN localization, similar to that shown for GEN in mammary epithelial cells. LUN-induced cellular apoptosis, akin to GEN, was mediated by PTEN, but unlike that for GEN, was p53-independent. LUN promoted E-cadherin and b-catenin nonnuclear localization similar to GEN, but unlike GEN, did not influence the proliferative effects of oncogene Wnt1 on HC11 cells. Further, LUN did not recapitulate GEN inhibitory effects on expansion of the cancer stem-like/ progenitor population in MCF-7 cells. Results suggest the concerted actions of GEN and LUN on cellular apoptosis for potential mammary tumor preventive effects and highlight whole food consumption rather than intake of specific dietary supplements with limited biological effects for greater health benefits.

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Section: Introductionmentioning

confidence: 99%

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

Pabona

Dave

et al. 2012

Genes Nutr

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“…Studies administering soy diets to transgenic mice have also shown conflicting results. A study by Chiesa et al [ 44 ] fed MMTV-neu transgenic mice a diet high in soy protein and soy isoflavones during gestation and lactation. At weaning, mice received a soy-free diet, a diet high in soy protein and soy isoflavones or a diet high in soy protein but containing low levels of soy isoflavones.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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BackgroundEpidemiologic data indicates that Asian diets, which are high in soy protein, reduce a women’s risk of developing breast cancer. However, it has been difficult to dissociate the benefits of soy from other variables including environmental and lifestyle factors. Since prospective studies in humans would take decades to complete, rodent models provide a valuable research alternative.MethodsIn this study, MTB-IGFIR transgenic mice, which develop mammary tumors resulting from overexpression of the type I insulin-like growth factor receptor (IGF-IR), were utilized. MTB-IGFIR mice were fed a soy-based or casein-based diet throughout all stages of development to reflect soy exposure in Asian cultures. Mammary tumors were initiated at 2 different developmental stages by commencing IGF-IR transgene expression either during puberty or in adult mice.ResultsMTB-IGFIR mice fed a soy-based diet displayed increased tumor incidence and accelerated tumor onset compared to MTB-IGFIR mice fed a casein diet. Two markers of estrogen receptor signaling, Pgr and Areg, were elevated in mammary tissue from mice fed the soy diet compared to mice fed the casein diet suggesting that high levels of soy may promote mammary tumor development through acting as an estrogen receptor agonist. Mammary tumors from mice fed a soy diet more frequently expressed metaplastic markers such as cytokeratins 5 and 14 as well as p63 and displayed reduced lung metastases compared to mammary tumors from mice fed a casein diet.ConclusionsDiets consisting of very high levels of soy protein promote mammary tumor development and decrease tumor latency possibly through activating estrogen receptor signaling. Additional studies are required to determine whether a more moderate amount of dietary soy can inhibit oncogene-induced mammary tumorigenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1037-z) contains supplementary material, which is available to authorized users.

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“…One study using MMTV- neu mice found that mice fed a diet containing the isoflavone-enriched product, Prevastein, had reduced tumor incidence and prolonged tumor latency in the group that were fed a high-fat diet based on corn oil, but not in the group with a diet based on fish oil. 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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Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone‐poor soy protein concentrate

Cited by 9 publications

References 68 publications

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

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

Rodent Models Assessing Mammary Tumor Prevention by Soy or Soy Isoflavones

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