乳腺癌细胞中 BAP1 的过表达对 Med1 蛋白的调控

IF 2.6 Q3 ONCOLOGY Molecular and Cellular Oncology Pub Date : 2024-05-02 eCollection Date: 2024-01-01 DOI:10.1080/23723556.2024.2347827
Hyunju Kim
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引用次数: 0

摘要

Med1 与核受体结合并调节转录。在激素依赖性乳腺癌和前列腺癌中,Med1 蛋白表达的升高会促进癌症的生长。通过在乳腺癌细胞系中过表达去泛素化酶(DUBs)来研究 Med1 蛋白的表达。在MCF7细胞系中过表达各种SRT-DUBs DNA构建体,并通过Western印迹法检测Med1蛋白的表达。在 BRCA1 相关蛋白 1(BAP1)野生型和突变型(C91A)过表达细胞中进行了细胞生长和体外侵袭试验。观察到了 Med1 蛋白的泛素化,并通过过表达的各种 DUBs 验证了 Med1 蛋白的表达和转录活性。虽然过表达 BAP1 会增加 Med1 蛋白的表达,但过表达 BAP1 突变体(C91A)并不影响 Med1 蛋白的表达。对乳腺癌生长有重要影响的 E2 处理会增加 BAP1 的表达,而 BAP1 C91A 的过表达会降低细胞的生长。然而,BAP1 的转移能力却降低了。此外,还观察到 Med1 与 BAP1 蛋白的结合。这些数据表明,BAP1能调控乳腺癌细胞中Med1蛋白的表达,并通过与Med1蛋白结合参与癌细胞的生长和转移。
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Regulation of Med1 protein by overexpression of BAP1 in breast cancer cells.

Med1 binds to a nuclear receptor and regulates transcription. Elevated Med1 protein expression promotes cancer growth in hormone-dependent breast and prostate cancers. Med1 protein expression was investigated by deubiquitinating enzymes (DUBs) overexpression in breast cancer cell lines. Various DNA constructs of SRT-DUBs were overexpressed in the MCF7 cell line, and Med1 protein expression was investigated by western blotting. The cell growth and in vitro invasion assay were performed in BRCA1-associated protein 1 (BAP1) wild type and mutant (C91A) overexpressed cells. Ubiquitination of the Med1 protein was observed, and Med1 protein expression and transcriptional activity were verified by various DUBs overexpressed. Although Med1 protein expression increased upon the overexpression of BAP1, it was not affected by the overexpression of BAP1 mutant (C91A). BAP1 was increased by the E2 treatment, which has an important effect on the breast cancer growth, and cell growth was decreased by BAP1 C91A overexpression. However, metastatic capacities were decreased by BAP1. In addition, the binding between the Med1 and the BAP1 protein was observed. These data suggested that BAP1 regulated Med1 protein expression in breast cancer cells and involved in cancer cell growth and metastasis by binding to Med1 protein.

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来源期刊
Molecular and Cellular Oncology
Molecular and Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
3.20
自引率
0.00%
发文量
18
期刊介绍: For a long time, solid neoplasms have been viewed as relatively homogeneous entities composed for the most part of malignant cells. It is now clear that tumors are highly heterogeneous structures that evolve in the context of intimate interactions between cancer cells and endothelial, stromal as well as immune cells. During the past few years, experimental and clinical oncologists have witnessed several conceptual transitions of this type. Molecular and Cellular Oncology (MCO) emerges within this conceptual framework as a high-profile forum for the publication of fundamental, translational and clinical research on cancer. The scope of MCO is broad. Submissions dealing with all aspects of oncogenesis, tumor progression and response to therapy will be welcome, irrespective of whether they focus on solid or hematological neoplasms. MCO has gathered leading scientists with expertise in multiple areas of cancer research and other fields of investigation to constitute a large, interdisciplinary, Editorial Board that will ensure the quality of articles accepted for publication. MCO will publish Original Research Articles, Brief Reports, Reviews, Short Reviews, Commentaries, Author Views (auto-commentaries) and Meeting Reports dealing with all aspects of cancer research.
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