Polo Andrea, Nittoli Chiara, Crispo Anna, Langastro Teresa, Cocco Stefania, Severino Lorella, De Laurentiis Michelino, Ciliberto Gennaro, Montella Maurizio, Budillon Alfredo, Costantini Susan
Epidemiology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
Mol Biosyst. 2017 Nov 21;13(12):2687-2696. doi: 10.1039/c7mb00489c.
Endocrine disrupting chemicals (EDCs) are natural or synthetic exogenous substances affecting human health. Although present at low concentrations in the environment, they can cause a broad range of negative effects on the endocrine functions by mimicking the action of steroid hormones due to their structural similarity. Hormonal unbalance can play an important role in carcinogenesis at any stage of disease. In the case of the breast cancer, EDCs directly affect the transformation of normal breast cells into cancer cells by interfering with hormonal regulation and by inducing the alteration of factors that regulate gene expression. The principal aims of this work were to study the interaction networks of proteins modulated in breast cancer by either environmental EDCs or mycotoxins, and to identify the proteins with the strongest coordination role defined as hub nodes. Our studies evidenced the presence of seven and six hub proteins in two EDCs and mycotoxins networks, respectively. Then, by merging the two networks, we identified that three hub nodes (BCL2, ESR2 and CTNNB1) in the environmental EDCs network show direct interactions with three hub nodes (CASP8, RELA and MKI67) in the mycotoxins network. These data highlighted that two networks are linked through proteins involved in the apoptosis regulation and in processes related to cell proliferation and survival, and, thus, in breast cancer progression.
内分泌干扰化学物质（EDCs）是影响人类健康的天然或合成外源性物质。尽管它们在环境中浓度较低，但由于其结构相似性，可通过模拟类固醇激素的作用对内分泌功能产生广泛的负面影响。激素失衡在疾病的任何阶段的致癌过程中都可能起重要作用。就乳腺癌而言，EDCs通过干扰激素调节并诱导调节基因表达的因子改变，直接影响正常乳腺细胞向癌细胞的转化。这项工作的主要目的是研究环境EDCs或霉菌毒素在乳腺癌中调节的蛋白质的相互作用网络，并确定具有最强协调作用的蛋白质，即枢纽节点。我们的研究分别证明了在两个EDCs和霉菌毒素网络中存在七个和六个枢纽蛋白。然后，通过合并这两个网络，我们发现环境EDCs网络中的三个枢纽节点（BCL2、ESR2和CTNNB1）与霉菌毒素网络中的三个枢纽节点（CASP8、RELA和MKI67）存在直接相互作用。这些数据突出表明，两个网络通过参与细胞凋亡调节以及与细胞增殖和存活相关过程的蛋白质相互连接，从而与乳腺癌进展相关。
