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首页> 外文期刊>Environmental research >Impact of endocrine disruptor hexachlorobenzene on the mammary gland and breast cancer: The story thus far
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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：乳腺癌发病率在全球范围内越来越大，暴露于内分泌破坏剂已成为潜在的危险因素的重要性。六氯苯（HCB）曾经用作杀真菌剂，尽管被禁止，但仍然释放到环境中。 HCB作为甲状腺，子宫和乳腺的内分泌破坏剂，分类为可能的致癌物体，该综述提供了对在过去15年的研究中获得的结果进行了彻底的分析，并评估了在多样化的乳腺和乳腺癌中的测定数据动物模型。我们讨论了环境相关HCB浓度对正常乳腺和不同癌症阶段的影响，并试图在分子水平下阐明其作用机制。 HCB弱粘合到芳基烃受体（AHR）中，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，修饰了涉及乳腺发生和乳腺癌发育的几种途径，诱导肿瘤进展。因此，HCB刺激了乳腺癌的上皮细胞增殖，促塑性病变和改变以及乳腺癌中的肿瘤细胞迁移和侵袭，转移和血管生成。总之，我们的研究结果支持假设HCB在高脂肪组织中的存在和生物累积以及在妊娠，儿童和青春期的高敏感时间窗口，使乳腺肿瘤发育的危险因素产生暴露。

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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;芳基烃受体;内分泌干扰器;

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