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Impact of endocrine disruptor hexachlorobenzene on the mammary gland and breast cancer: The story thus far

机译：内分泌干​​扰物六氯苯对乳腺和乳腺癌的影响：迄今为止的故事

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摘要

Breast cancer incidence is increasing globally and exposure to endocrine disruptors has gained importance as a potential risk factor. Hexachlorobenzene (HCB) was once used as a fungicide and, despite being banned, considerable amounts are still released into the environment. HCB acts as an endocrine disruptor in thyroid, uterus and mammary gland and was classified as possibly carcinogenic to human This review provides a thorough analysis of results obtained in the last 15 years of research and evaluates data from assays in mammary gland and breast cancer in diverse animal models. We discuss the effects of environmentally relevant HCB concentrations on the normal mammary gland and different stages of carcinogenesis, and attempt to elucidate its mechanisms of action at molecular level. HCB weakly binds to the aryl hydrocarbon receptor (AhR), activating both membrane (c-Src) and nuclear pathways. Through c-Src stimulation, AhR signaling interacts with other membrane receptors including estrogen receptor-alpha, insulin-like growth factor-1 receptor, epidermal growth factor receptor and transforming growth factor beta 1 receptors. In this way, several pathways involved in mammary morphogenesis and breast cancer development are modified, inducing tumor progression. HCB thus stimulates epithelial cell proliferation, preneoplastic lesions and alterations in mammary gland development as well as neoplastic cell migration and invasion, metastasis and angiogenesis in breast cancer. In conclusion, our findings support the hypothesis that the presence and bioaccumulation of HCB in high-fat tissues and during highly sensitive time windows such as pregnancy, childhood and adolescence make exposure a risk factor for breast tumor development.
机译：乳腺癌在全球范围内的发病率正在上升，暴露于内分泌干扰物已成为潜在的危险因素。六氯苯（HCB）曾经被用作杀真菌剂，尽管被禁止，但仍有相当多的量释放到环境中。 HCB在甲状腺，子宫和乳腺中起内分泌干扰物的作用，被分类为可能致癌的物质。这篇综述对过去15年的研究结果进行了全面分析，并评估了各种乳腺和乳腺癌试验的数据动物模型。我们讨论了与环境有关的六氯代苯浓度对正常乳腺和癌变不同阶段的影响，并试图在分子水平上阐明其作用机理。 HCB弱结合芳烃受体（AhR），激活膜（c-Src）和核途径。通过c-Src刺激，AhR信号传导与其他膜受体相互作用，包括雌激素受体α，胰岛素样生长因子1受体，表皮生长因子受体和转化生长因子β1受体。以这种方式，改变了参与乳腺形态发生和乳腺癌发展的几种途径，从而诱导了肿瘤的进展。因此，六氯苯可刺激乳腺癌中的上皮细胞增殖，肿瘤前病变和乳腺发育改变，以及肿瘤细胞迁移和侵袭，转移及血管生成。总之，我们的发现支持以下假设：HCB在高脂肪组织中以及在高度敏感的时间窗（例如怀孕，童年和青春期）中的存在和生物蓄积，使暴露成为乳腺癌发展的危险因素。

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  • 来源
    《Environmental research》 |2019年第6期|330-341|共12页
  • 作者

    Miret Noelia V.; Pontillo Carolina A.; Zarate Lorena V.; Kleiman de Pisarev Diana; Cocca Claudia; Randi Andrea S.;

  • 作者单位

    Univ Buenos Aires, Fac Med, Dept Bioquim Humana, Lab Efectos Biol Contaminantes Ambientales, Paraguay 2155,5to Piso,CP1121, Buenos Aires, DF, Argentina;

    Univ Buenos Aires, Fac Med, Dept Bioquim Humana, Lab Efectos Biol Contaminantes Ambientales, Paraguay 2155,5to Piso,CP1121, Buenos Aires, DF, Argentina;

    Univ Buenos Aires, Fac Med, Dept Bioquim Humana, Lab Efectos Biol Contaminantes Ambientales, Paraguay 2155,5to Piso,CP1121, Buenos Aires, DF, Argentina;

    Univ Buenos Aires, Fac Med, Dept Bioquim Humana, Lab Efectos Biol Contaminantes Ambientales, Paraguay 2155,5to Piso,CP1121, Buenos Aires, DF, Argentina;

    Univ Buenos Aires, Fac Farm & Bioquim, Lab Radioisotopos, Junin 954,Subsuelo,CP1113, Buenos Aires, DF, Argentina;

    Univ Buenos Aires, Fac Med, Dept Bioquim Humana, Lab Efectos Biol Contaminantes Ambientales, Paraguay 2155,5to Piso,CP1121, Buenos Aires, DF, Argentina;

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  • 正文语种 eng
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  • 关键词

    Hexachlorobenzene; Mammary gland; Breast cancer; Aryl hydrocarbon receptor; Endocrine disruptor;

    机译：六氯苯;乳腺;乳腺癌;芳烃受体;内分泌干扰物;

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