Austin David, Hamilton Nalo, Elshimali Yahya, Pietras Richard, Wu Yanyuan, Vadgama Jaydutt
Department of Medicine, Division of Cancer Research and Training, Charles Drew University School of Medicine and Science, Los Angeles, CA 90059, USA.
UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Oncotarget. 2018 Sep 21;9(74):33912-33930. doi: 10.18632/oncotarget.26089.
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.
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，缺乏雌激素受体（ER）、孕激素受体和人表皮生长因子受体2的表达。TNBC占所有乳腺癌病例的15%-20%，但占死亡率的50%以上。我们提出，雌激素受体β（ERβ）和胰岛素样生长因子2（IGF2）在TNBC的发病机制中起重要作用，可能是未来治疗的重要靶点。通过免疫组织化学分析了250多名TNBC患者的组织微阵列（TMA）中ERβ和IGF2的表达。表达与临床结果相关。此外，使用TNBC细胞系高加索人（CA）：MB-231/BT549和非裔美国人（AA）：MB-468/HCC70/HCC1806来研究激素和生长因子调节对细胞增殖的影响。与CA相比，AA的TMA中ERβ和IGF2表达更高。与其他细胞类型相比，我们的TNBC细胞系中ERβ和IGF2被发现上调。与对照组相比，用ERβ激动剂处理的TNBC细胞在细胞增殖和迁移方面显示出显著增加。TNBC患者的AA组织样本中ERβ表达更高。TNBC患者的非裔美国乳腺癌TNBC组织样本中ERβ表达更高。此外，还发现TNBC细胞系也表达高水平的ERβ。IGF2增加TNBC细胞中ERβ的转录。了解TNBC肿瘤中IGF2/ERβ轴的机制可能为靶向这种侵袭性乳腺癌亚型提供机会。
