Canine mammary gland tumors (CMTs) are the most common tumor type in female dogs. This study evaluated the expression pattern and role of thyroglobulin (Tg) in CMT and in human breast cancer (HBC). CMT samples were subjected to fine-needle aspiration, primary cell culture, and histopathology. The expression level of Tg was higher in benign CMT than in malignant CMT (mCMT) primary cells, particularly in the epithelial lineage. Moreover, treatment with Tg enhanced the sensitivity of doxorubicin in mCMT epithelial cells and mitigated proinflammatory response by increasing nuclear factor erythroid 2-related factor 2 (Nrf2). The proximal region of the Tg promoter was hypermethylated in mCMT epithelial cells, silencing Tg expression with concurrent downregulation of Nrf2-mediated antioxidant signaling. An identical pattern of Tg expression was observed in cytological and tissue samples. Tissue microarray analysis showed that Tg was highly expressed in normal and benign tissues when compared with their malignant counterparts, which was diminished along with higher histological grades. The survival rate was significantly higher in HBC patients with high Tg expression than those with low Tg expression. This study also showed that the progression of HBC is accompanied by the reduction of Tg expression along with augmentation of proinflammatory signaling. Our data suggested that Tg could be a negative indicator of malignancy in canine and human breast neoplasia

中文翻译：

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甲状腺球蛋白作为犬和人类乳腺肿瘤恶性的阴性标志物

犬乳腺肿瘤 (CMT) 是母犬中最常见的肿瘤类型。本研究评估了甲状腺球蛋白 (Tg) 在 CMT 和人类乳腺癌 (HBC) 中的表达模式和作用。CMT 样本进行细针抽吸、原代细胞培养和组织病理学。Tg 在良性 CMT 中的表达水平高于恶性 CMT (mCMT) 原代细胞，尤其是在上皮谱系中。此外，Tg 治疗增强了 mCMT 上皮细胞中阿霉素的敏感性，并通过增加核因子红细胞 2 相关因子 2 (Nrf2) 来减轻促炎反应。Tg 启动子的近端区域在 mCMT 上皮细胞中被高甲基化，使 Tg 表达沉默，同时下调 Nrf2 介导的抗氧化信号。在细胞学和组织样本中观察到相同的 Tg 表达模式。组织微阵列分析表明，与恶性组织相比，Tg 在正常和良性组织中高表达，随着组织学分级的升高而降低。高 Tg 表达的 HBC 患者的存活率明显高于低 Tg 表达的 HBC 患者。该研究还表明，HBC 的进展伴随着 Tg 表达的降低以及促炎信号的增强。我们的数据表明 Tg 可能是犬类和人类乳腺肿瘤恶性程度的阴性指标 这随着更高的组织学等级而减少。高 Tg 表达的 HBC 患者的存活率明显高于低 Tg 表达的 HBC 患者。该研究还表明，HBC 的进展伴随着 Tg 表达的降低以及促炎信号的增强。我们的数据表明 Tg 可能是犬类和人类乳腺肿瘤恶性程度的阴性指标 这随着更高的组织学等级而减少。高 Tg 表达的 HBC 患者的存活率明显高于低 Tg 表达的 HBC 患者。该研究还表明，HBC 的进展伴随着 Tg 表达的降低以及促炎信号的增强。我们的数据表明 Tg 可能是犬类和人类乳腺肿瘤恶性程度的阴性指标