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雌激素受体α在蛋白质水平对乳腺癌中FOXM1转录因子的调控

Regulation of the FOXM1 transcription factor by the estrogen receptor alpha at the protein level, in breast cancer.

作者信息

Karadedou C T

机构信息

Department of Molecular Oncology, Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College London.

出版信息

Hippokratia. 2006 Jul;10(3):128-32.

Abstract

Breast cancer is the most frequent type of cancer of women in the western world. Antiestrogens, including Tamoxifen (OHT) and Faslodex (ICI), are widely used in the endocrine treatment of breast cancer. However, the majority of breast cancers are either resistant to endocrine therapy or eventually become unresponsive to antiestrogen therapy. Better understanding of the molecular mechanisms that govern tumour proliferation, is therefore needed to develop new therapies for the disease. The Forkhead family of transcription factors plays an important role in regulating cell proliferation, cell death and differentiation.The estrogen receptor (ER) a positive breast carcinoma cell line MCF-7 and the ERa negative line MDA-MB-231 was used to study the potential regulation of the Forkhead member FOXM1 by ER. It was indicated that estrogen and ER regulate the expression of FOXM1 at the protein level. Since Forkhead proteins play an important role in regulating cell proliferation, cell death and differentiation, this study helps to explain some of the functions of ER in tumourigenesis, and the way these Forkhead proteins could be crucial targets for therapeutic strategies and/or markers for diagnosis and prognosis.

摘要

在西方世界,乳腺癌是女性中最常见的癌症类型。抗雌激素药物,包括他莫昔芬(OHT)和氟维司群(ICI),被广泛用于乳腺癌的内分泌治疗。然而,大多数乳腺癌要么对内分泌治疗耐药,要么最终对抗雌激素治疗无反应。因此,需要更好地了解控制肿瘤增殖的分子机制,以开发针对该疾病的新疗法。叉头转录因子家族在调节细胞增殖、细胞死亡和分化中起重要作用。雌激素受体(ER)α阳性乳腺癌细胞系MCF-7和ERα阴性细胞系MDA-MB-231被用于研究ER对叉头家族成员FOXM1的潜在调控。结果表明,雌激素和ER在蛋白质水平上调节FOXM1的表达。由于叉头蛋白在调节细胞增殖、细胞死亡和分化中起重要作用,本研究有助于解释ER在肿瘤发生中的一些功能,以及这些叉头蛋白可能成为治疗策略的关键靶点和/或诊断及预后标志物的方式。

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