Relationship between RUNX1 and AXIN1 in ER-negative versus ER-positive Breast Cancer
Relationship between RUNX1 and AXIN1 in ER-negative versus ER-positive Breast Cancer
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DOI：
10.1080/15384101.2016.1237325
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Frenkel, Baruch
中科院分区：
文献类型：
--
作者：
Chimge, Nyam-Osor;Ahmed-Alnassar, Sara;Frenkel, Baruch
RUNX 1在乳腺癌中起着相反的作用：雌激素受体阳性（ER+）疾病中的肿瘤抑制剂和ER阴性（ER-）肿瘤中的致癌作用。潜在地介导前者，我们最近报道RUNX 1阻止雌激素驱动的抑制编码肿瘤抑制因子AXIN 1的mRNA。因此，在ER+乳腺癌细胞中RUNX 1沉默后，AXIN 1蛋白表达减少，并且在具有高水平ER的肿瘤中与AXIN 1蛋白表达正相关。在这里，我们报告了令人惊讶的观察结果，即RUNX 1和AXIN 1蛋白在ER肿瘤中也密切相关。然而，这种相关性并不归因于RUNX 1对AXIN 1的调节，反之亦然。在ER-乳腺癌中发挥致癌作用的RUNX 1与已确立的肿瘤抑制中心AXIN 1之间的意外相关性可能与ER-乳腺癌中AXIN 1的变体2和变体1（v2/v1）的表达比率高于ER+乳腺癌有关。虽然这两种亚型在雌激素刺激的ER+乳腺癌细胞中受到RUNX 1的类似调节，但ER-疾病中较高的v2/v1比率预计会削弱AXIN 1在这些肿瘤中的肿瘤抑制活性。
RUNX1 plays opposing roles in breast cancer: a tumor suppressor in estrogen receptor-positive (ER+) disease and an oncogenic role in ER-negative (ER-) tumors. Potentially mediating the former, we have recently reported that RUNX1 prevents estrogen-driven suppression of the mRNA encoding the tumor suppressor AXIN1. Accordingly, AXIN1 protein expression was diminished upon RUNX1 silencing in ER+ breast cancer cells and was positively correlated with AXIN1 protein expression across tumors with high levels of ER. Here we report the surprising observation that RUNX1 and AXIN1 proteins are strongly correlated in ER- tumors as well. However, this correlation is not attributable to regulation of AXIN1 by RUNX1 or vice versa. The unexpected correlation between RUNX1, playing an oncogenic role in ER- breast cancer, and AXIN1, a well-established tumor suppressor hub, may be related to a high ratio between the expression of variant 2 and variant 1 (v2/v1) of AXIN1 in ER- compared with ER+ breast cancer. Although both isoforms are similarly regulated by RUNX1 in estrogen-stimulated ER+ breast cancer cells, the higher v2/v1 ratio in ER- disease is expected to weaken the tumor suppressor activity of AXIN1 in these tumors.