ERα increases endometrial cancer cell resistance to cisplatin via upregulation of BAG3.

ERα increases endometrial cancer cell resistance to cisplatin via upregulation of BAG3.
复制标题

ERα通过上调BAG3增加了子宫内膜癌细胞对顺铂的耐药性。

DOI:
10.3892/ol.2020.12281
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发表时间:
2021-01
期刊:
影响因子:
2.9
通讯作者:
Saito T
Saito T
中科院分区:
医学4区
文献类型:
--
作者:
Abe S;Iwasaki M;Habata S;Mariya T;Tamate M;Matsuura M;Satohisa S;Saito T

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子宫内膜癌是女性癌症相关死亡的主要原因,并且晚期预后不良。我们之前的研究表明,BCL-2 相关的 athanogene 3 (BAG3) 可能通过下调子宫内膜癌细胞系中的 microRNA (miR)-29b 来增强细胞活力。此外,最近报道了几种癌细胞类型中雌激素受体 α (ERα) 和 BAG3 之间的关系。本研究调查了子宫内膜癌细胞系中ERα和BAG3之间的关系。结果表明,外源性ERα过表达增强了不内源表达ERα的EMTOKA子宫内膜癌细胞系中BAG3的表达,但对内源表达ERα的Ishikawa细胞系中的BAG3表达水平没有影响。此外,在 EMTOKA 细胞中,ERα 过表达抑制 miR-29b 表达,并增强 Mcl-1(一种位于 BAG3 下游的介质)的表达,但在 Ishikawa 细胞中则不然。在顺铂存在下,ERα 过表达也增强了 EMTOKA(但不是 Ishikawa)子宫内膜癌细胞的活力。这些发现表明,ERα可能通过BAG3过度表达增强子宫内膜癌细胞对抗癌药物的抵抗力。
Endometrial cancer is a leading cause of cancer-associated mortality in women and has a poor prognosis in advanced stages. Our previous study revealed that BCL-2-associated athanogene 3 (BAG3) may contribute to enhancing cell viability through downregulation of microRNA (miR)-29b in endometrial cancer cell lines. In addition, a relationship between estrogen receptor α (ERα) and BAG3 was recently reported in several cancer cell types. The present study investigated the relationship between ERα and BAG3 in endometrial cancer cell lines. The results demonstrated that exogenous ERα overexpression enhanced BAG3 expression in the EMTOKA endometrial cancer cell line, which does not endogenously express ERα, but had no effect on BAG3 expression levels in the Ishikawa cell line, which does endogenously express ERα. In addition, ERα overexpression suppressed miR-29b expression and enhanced the expression of Mcl-1, a mediator situated downstream of BAG3, in EMTOKA cells, but not Ishikawa cells. ERα overexpression also enhanced EMTOKA, but not Ishikawa, endometrial cancer cell viability in the presence of cisplatin. These findings suggested that ERα may contribute to enhancing endometrial cancer cell resistance to anticancer agents through BAG3 overexpression.
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