Bernichtein Sophie, Pigat Natascha, Capiod Thierry, Boutillon Florence, Verkarre Virginie, Camparo Philippe, Viltard Mélanie, Méjean Arnaud, Oudard Stéphane, Souberbielle Jean-Claude, Friedlander Gérard, Goffin Vincent
Inserm, U1151, Institut Necker Enfants Malades, PRL/GH Pathophysiology Laboratory, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
Pathology Department, Hôpital Necker, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Assistance Publique Hôpitaux de Paris, Paris, France.
PLoS One. 2015 May 4;10(5):e0125423. doi: 10.1371/journal.pone.0125423. eCollection 2015.
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.
调查乳制品（主要是牛奶）饮食是否与前列腺癌风险相关的流行病学研究得出了有争议的结论。此外，现有的研究均未明确评估乳制品/牛奶饮食对前列腺肿瘤进展的影响，鉴于全球数百万患有前列腺疾病（包括良性前列腺增生（BPH）或高级别前列腺上皮内瘤变（HGPIN））的男性，这在临床上具有高度相关性。我们在此报告一项独特的干预性动物研究以解决此问题。我们使用了两种完全穿透性基因诱导前列腺肿瘤发生的小鼠模型，分别在良性增生阶段（前列腺素 - Prl小鼠，Pb - Prl）或癌前PIN病变阶段（KIMAP小鼠）进行研究。根据每个模型中前列腺肿瘤发展的动力学，给小鼠喂食高牛奶饮食（脱脂或全脂）15至27周。通过组织组织病理学检查、上皮增殖、基质炎症和纤维化、肿瘤侵袭力以及与每个模型相关的各种肿瘤标志物（c - Fes、Gprc6a、活化的Stat5和p63）的表达来评估前列腺肿瘤进展。我们的结果表明，在肿瘤发生的早期阶段（增生和瘤变）进行评估时，高牛奶摄入量（脱脂或全脂）不会促进现有前列腺肿瘤的进展。对于某些参数，并且取决于牛奶类型，牛奶饮食甚至可以通过降低肿瘤相关标志物如Ki - 67和Gprc6a的表达，对前列腺肿瘤进展表现出轻微的保护作用。总之，我们的研究表明，对于患有早期前列腺肿瘤的患者，不应认为经常饮用牛奶有害。
