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雌激素通过下调 CPEB1 表达促进乳腺癌细胞增殖和迁移。

Estrogen promotes increased breast cancer cell proliferation and migration through downregulation of CPEB1 expression.

机构信息

Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.

Department of Breast Surgery, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-cho, Ibaraki, 300-0395, Japan.

出版信息

Biochem Biophys Res Commun. 2021 Jan 1;534:871-876. doi: 10.1016/j.bbrc.2020.10.085. Epub 2020 Nov 6.

Abstract

The polyadenylation element binding protein 1 (CPEB1) plays an important role in the regulation of poly(A) tail length at the 3'UTR of mRNA during transcription. Downregulation of CPEB1 expression, which is associated with the loss of mammary epithelial polarity, has been reported in breast cancer. CPEB1 downregulation leads to an increase in tumor aggressiveness of breast cancer. Breast cancer is also known to be responsive to the treatment with steroid hormones, which promotes cancer development and progression; however, the nature of these associations remains unclear. This study aimed to investigate whether estrogen and progesterone impacted CPEB1 expression in breast cancer in order to regulate cell proliferation and migration. MCF7 cell proliferation was increased in response to estrogen treatment, and estrogen application suppressed the expression of CPEB1 mRNA. Cells treated with estrogen or those depleted for CPEB1 by shRNA showed increased wound healing capacity compared with that of control cells in migration assay. Moreover, we found that CPEB1 level of expression in human breast cancer tissue was low compared with that in the healthy tissue. CPEB1 expression was downregulated in response to estrogen activity and in turn, that caused a significantly induced cell migration in breast cancer cells. This suggests that CPEB1 is one of the estrogen responsive genes, which stimulates breast cancer progression. Increasing and/or maintaining CPEB1 expression level has the potential to control breast cancer behavior.

摘要

多聚腺苷酸化元件结合蛋白 1(CPEB1)在转录过程中 mRNA 3'UTR 的多聚(A)尾长度的调节中发挥重要作用。乳腺癌中报道了 CPEB1 表达下调与乳腺上皮极性丧失有关。CPEB1 下调导致乳腺癌的肿瘤侵袭性增加。乳腺癌也已知对类固醇激素的治疗有反应,这促进了癌症的发展和进展;然而,这些关联的性质仍不清楚。本研究旨在研究雌激素和孕激素是否会影响乳腺癌中的 CPEB1 表达,以调节细胞增殖和迁移。雌激素处理增加 MCF7 细胞增殖,雌激素应用抑制 CPEB1 mRNA 的表达。与对照细胞相比,用雌激素处理或用 shRNA 耗尽 CPEB1 的细胞在迁移试验中显示出更高的伤口愈合能力。此外,我们发现人乳腺癌组织中的 CPEB1 表达水平低于健康组织。CPEB1 表达受雌激素活性下调,进而导致乳腺癌细胞中显著诱导的细胞迁移。这表明 CPEB1 是雌激素反应基因之一,可刺激乳腺癌进展。增加和/或维持 CPEB1 表达水平有可能控制乳腺癌的行为。

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