针对特殊AT-rich序列结合蛋白1的诱饵dna抑制人乳腺癌的生长和侵袭能力。

Asako Yamayoshi, Mariko Yasuhara, Sanjeev Galande, Akio Kobori, Akira Murakami
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引用次数: 18

摘要

“三阴性”(TN)乳腺癌的特征是雌激素受体(-)、孕激素受体(-)和人表皮生长因子受体2(-),由于其侵袭性的肿瘤表型,通常与预后不良相关。近年来,乳腺癌患者数量显著增加,但可用于治疗TN型乳腺癌的药物却很少。迫切需要开发针对TN型乳腺癌的新型药物。在本研究中,我们重点研究了特殊AT-rich sequence binding protein 1 (SATB1)作为靶分子在TN乳腺癌治疗中的作用。通过募集染色质重塑酶和转录因子,SATB1调控了超过1000个与细胞生长和易位相关的基因的表达。我们合成了一个针对SATB1的诱饵DNA,包括SATB1的识别序列。我们研究了诱饵dna对TN转移性乳腺癌细胞系(MDA-MB-231)细胞增殖的抑制作用。satb1诱饵DNA抑制MDA-MB-231细胞的增殖。特别值得注意的是,satb1诱饵DNA显著降低了MBA-MB-231细胞的侵袭和转移能力。此外,在MCF7细胞(satb1阴性乳腺癌细胞系)中,satb1诱饵DNA没有表现出任何抑制作用。这些数据表明,satb1诱饵DNA可能是一种有效的候选分子靶向药物,可用于治疗TN乳腺癌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoy-DNA against special AT-rich sequence binding protein 1 inhibits the growth and invasive ability of human breast cancer.

"Triple-negative" (TN) breast cancers, which are characterized by estrogen receptor (-), progesterone receptor (-), and human epidermal growth factor receptor 2 (-), are typically associated with poor prognosis because of their aggressive tumor phenotypes. In recent years, the number of patients with breast cancers has remarkably increased, but there are only few available drugs for treatment of TN breast cancers. The development of novel drugs targeting TN breast cancer is urgently required. In the present study, we focused on the function of special AT-rich sequence binding protein 1 (SATB1) as a target molecule for the treatment of TN breast cancers. By recruiting chromatin remodeling enzymes and transcriptional factors, SATB1 regulates the expression of >1,000 genes related to cell growth and translocation. We synthesized a decoy DNA against SATB1, including the recognition sequence of SATB1. We examined the inhibitory effects of the decoy DNAs on cellular proliferation of a TN metastatic breast cancer cell line (MDA-MB-231). SATB1-decoy DNA inhibited the proliferation of MDA-MB-231 cells. Especially, it was significant that SATB1-decoy DNA drastically reduced the invasive and metastatic capacity of MBA-MB-231 cells. Further, in the case of MCF7 cells (SATB1-negative breast cancer cell line), SATB1-decoy DNA did not exhibit any inhibitory effect. These data suggest that SATB1-decoy DNA may be an effective candidate for use as a molecular-targeting drug for treatment of TN breast cancer.

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Oligonucleotides
Oligonucleotides 生物-生化与分子生物学
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