A Milk Protein, Casein, as a Proliferation Promoting Factor in Prostate Cancer Cells

Park, Sung Woo; Kim, Joo Young; Kim, You Sun; Lee, Sang Jin; Chung, Moon Kee

doi:10.5534/wjmh.2014.32.2.76

Cited by 19 publications

(15 citation statements)

References 27 publications

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“…At best, a recent in vitro study reporting that caseins (typical milk proteins) could promote proliferation of PC3 and LNCaP prostate cancer cells argues against our results. However, these effects i) were obtained at extremely high casein concentration (1 mg/mL), ii) were not validated in vivo [ 38 ], and iii) only involved a single milk protein family out of the complex nature of ingredients constituting milk. Taken together, it is fair to claim that, globally, milk does not promote prostate tumor progression in Pb-Prl and KIMAP mice.…”

Section: Discussionmentioning

confidence: 99%

High Milk Consumption Does Not Affect Prostate Tumor Progression in Two Mouse Models of Benign and Neoplastic Lesions

et al. 2015

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Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.

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Section: Discussionmentioning

confidence: 99%

High Milk Consumption Does Not Affect Prostate Tumor Progression in Two Mouse Models of Benign and Neoplastic Lesions

et al. 2015

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“…On the other hand, some studies drew opposite conclusions. Park et al confirmed that the milk protein casein promoted the proliferation of prostate cancer cells through in vitro assay [ 6 ]. Kroenke et al harbored the view that high-fat dairy intake was associated with poor prognosis after breast cancer diagnosis, however no significant effect was found with respect to low-fat dairy intake [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Dairy products intake and cancer mortality risk: a meta-analysis of 11 population-based cohort studies

Lü

Chen

Niu

et al. 2016

Nutr J

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BackgroundDairy products are major components of daily diet and the association between consumption of dairy products and public health issues has captured great attention. In this study, we conducted a meta-analysis to investigate the association between dairy products intake and cancer mortality risk.MethodsAfter a literature search in PubMed and EMBASE, 11 population-based cohort studies involving 778,929 individuals were considered eligible and included in the analyses. Data were extracted and the association between dairy products intake and cancer mortality risk was estimated by calculating pooled relative risks (RRs) and corresponding 95 % confidence intervals (CIs). Sensitivity analyses and subgroup analyses based on regions, genders and dairy types were performed as well. Potential dose–response relationship was further explored by adopting the generalized least squares (GLST) method.ResultsTotal dairy products intake was not associated with all cancer mortality risk, with the pooled RR of 0.99 (95 % CI 0.92–1.07, p = 0.893). Subgroup analyses showed that the pooled RRs were 0.97 (95 % CI 0.92–1.03, p = 0.314) for milk, 0.88 (95 % CI 0.71–1.10, p = 0.271) for yogurt, 1.23 (95 % CI 0.94–1.61, p = 0.127) for cheese and 1.13 (95 % CI 0.89–1.44, p = 0.317) for butter in male and female, however the pooled RR was 1.50 (95 % CI 1.03–2.17, p = 0.032) for whole milk in male, which was limited to prostate cancer. Further dose–response analyses were performed and we found that increase of whole milk (serving/day) induced elevated prostate cancer mortality risk significantly, with the RR of 1.43 (95 % CI 1.13–1.81, p = 0.003).ConclusionsTotal dairy products intake have no significant impact on increased all cancer mortality risk, while low total dairy intake even reduced relative risk based on the non-linear model. However, whole milk intake in men contributed to elevated prostate cancer mortality risk significantly. Furthermore, a linear dose–response relationship existed between increase of whole milk intake and increase of prostate cancer mortality risk.

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“…Nevertheless, most of the reviews point to a positive association between milk consumption and the incidence or increase of PC risk. However, there is strong evidence in the literature (not reviews) that associates dairy consumption and PC (91) and disease progression (82, 133), and possibly initialization (82). Through this review of the literature we understand the different mechanisms triggered by nutrients contained in milk and derivatives that may lead to an increased risk of prostate cancer in its consumers.…”

Section: Discussionmentioning

confidence: 99%

Dairy Products: Is There an Impact on Promotion of Prostate Cancer? A Review of the Literature

et al. 2019

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This review of the literature aims to study potential associations between high consumption of milk and/or dairy products and prostate cancer (PC). Literature is scarce, yet there is a direct relationship between mTORC1 activation and PC; several ingredients in milk/dairy products, when in high concentrations, increase signaling of the mTORC1 pathway. However, there are no studies showing an unequivocal relationship between milk products PC initiation and/or progression. Three different reviews were conducted with articles published in the last 5 years: (M1) PC and intake of dairy products, taking into account the possible mTORC1signaling mechanism; (M2) Intake of milk products and incidence/promotion of PC; (M3) mTORC1 activation signaling pathway, levels of IGF-1 and PC; (M4) mTORC pathway and dairy products. Of the 32 reviews identified, only 21 met the inclusion criteria and were analyzed. There is little scientific evidence that directly link the three factors: incidence/promotion of PC, intake of dairy products and PC, and PC and increased mTORC1 signaling. Persistent hyper-activation of mTORC1 is associated with PC promotion. The activity of exosomal mRNA in cellular communication may lead to different impacts of different types of milk and whether or not mammalian milks will have their own characteristics within each species. Based on this review of the literature, it is possible to establish a relationship between the consumption of milk products and the progression of PC; we also found a possible association with PC initiation, hence it is likely that the intake of dairy products should be reduced or minimized in mens' diet.

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A Milk Protein, Casein, as a Proliferation Promoting Factor in Prostate Cancer Cells

Cited by 19 publications

References 27 publications

High Milk Consumption Does Not Affect Prostate Tumor Progression in Two Mouse Models of Benign and Neoplastic Lesions

High Milk Consumption Does Not Affect Prostate Tumor Progression in Two Mouse Models of Benign and Neoplastic Lesions

Dairy products intake and cancer mortality risk: a meta-analysis of 11 population-based cohort studies

Dairy Products: Is There an Impact on Promotion of Prostate Cancer? A Review of the Literature

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