Identification of potential molecular pathways involved in prostate carcinogenesis in offspring exposed to maternal malnutrition

鉴定暴露于母亲营养不良的后代前列腺癌发生的潜在分子途径

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作者:Sérgio Alexandre Alcantara Santos, Ana Carolina Lima Camargo, Flávia Bessi Constantino, Ketlin Thassiani Colombelli, Luiz Marcos Frediani Portela, Matheus Naia Fioretto, José Cavalcante Souza Vieira, Pedro Magalhães Padilha, Mateus Betta de Oliveira, Sergio Luis Felisbino, Robson Francisco Carvalho,

Abstract

The developmental origins of health and disease concept links adult diseases with early-life exposure to inappropriate environmental conditions. Intrauterine and postnatal malnutrition may lead to an increased incidence of type 2 diabetes, obesity, and cardiovascular diseases. Maternal malnutrition (MM) has also been associated with prostate carcinogenesis. However, the molecular mechanisms associated with this condition remain poorly understood. Using a proteomic analysis, we demonstrated that MM changed the levels of proteins associated with growth factors, estrogen signaling, detoxification, and energy metabolism in the prostate of both young and old rats. These animals also showed increased levels of molecular markers of endoplasmic reticulum function and histones. We further performed an in silico analysis that identified commonly deregulated proteins in the ventral prostate of old rats submitted to MM with a mouse model and patients with prostate cancer. In conclusion, our results demonstrated that estrogenic signaling pathways, endoplasmic reticulum functions, energy metabolism, and molecular sensors of protein folding and Ca2+ homeostasis, besides histone, and RAS-GTPase family appear to be involved in this process. Knowledge of these factors may raise discussions regarding the role of maternal dietary intervention as a public policy for the lifelong prevention of chronic diseases.

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