Estrogen receptor-beta is a potential target for triple negative breast cancer treatment.
Estrogen receptor-beta is a potential target for triple negative breast cancer treatment.
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DOI：
10.18632/oncotarget.26089
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发表时间：
2018-09-21
期刊：
影响因子：
--
通讯作者：
Vadgama J
中科院分区：
文献类型：
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作者：
Austin D;Hamilton N;Elshimali Y;Pietras R;Wu Y;Vadgama J
三阴性乳腺癌（TNBC）是一种缺乏雌激素受体（ER）、孕酮受体和人表皮生长因子受体2表达的乳腺癌亚型。TNBC占所有乳腺癌病例的15-20%，但占死亡率的50%以上。我们认为雌激素受体β（ERβ）和IGF 2在TNBC的发病机制中起重要作用，并可能成为未来治疗的重要靶点。通过免疫组织化学方法分析了来自超过250例TNBC患者的组织微阵列（TMA）的ERβ和IGF 2表达。表达与临床结果相关。此外，TNBC细胞系高加索人（CA）：MB-231/BT549和非洲裔美国人（AAs）：MB-468/HCC 70/HCC 1806用于研究激素和生长因子调节对细胞增殖的影响。与CA相比，来自AA的TMA具有更高的ERβ和IGF 2表达。与其他细胞类型相比，发现ERβ和IGF 2在我们的TNBC细胞系中上调。当与对照相比时，用ERβ激动剂处理的TNBC细胞显示出细胞增殖和迁移的显著增加。TNBC患者的AA组织样本ERβ表达较高。来自TNBC患者的非裔美国人乳腺癌TNBC组织样品具有更高的ERβ表达。此外，还发现TNBC细胞系表达高水平的ERβ。IGF 2可增加TNBC细胞ERβ的转录。了解TNBC肿瘤中IGF 2/ERβ轴的机制可以为靶向这种侵袭性乳腺癌亚型提供机会。
Triple Negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2. TNBC accounts for 15-20% of all breast cancer cases but accounts for over 50% of mortality. We propose that Estrogen receptor-beta (ERβ) and IGF2 play a significant role in the pathogenesis of TNBCs, and could be important targets for future therapy. Tissue microarrays (TMAs) from over 250 TNBC patients' were analyzed for ERβ and IGF2 expression by immunohistochemistry. Expression was correlated with clinical outcomes. In addition, TNBC cell lines Caucasians (CA): MB-231/BT549 and African Americans (AAs): MB-468/HCC70/HCC1806 were used to investigate the effect of hormonal and growth factor regulation on cell proliferation. TMAs from AAs had higher expression of ERβ and IGF2 expression when compared to CA. ERβ and IGF2 were found to be upregulated in our TNBC cell lines when compared to other cell types. TNBC cells treated with ERβ agonist displayed significant increase in cell proliferation and migration when compared to controls. AA tissue samples from TNBC patients had higher expression of ERβ. African-American breast cancer TNBC tissue samples from TNBC patients have higher expression of ERβ. In addition, TNBC cell lines were also found to express high levels of ERβ. IGF2 increased transcription of ERβ in TNBC cells. Understanding the mechanisms of IGF2/ERβ axis in TNBC tumors could provide an opportunity to target this aggressive subtype of breast cancer.