Yamayoshi Asako, Yasuhara Mariko, Galande Sanjeev, Kobori Akio, Murakami Akira
Department of Biomolecular Engineering, Kyoto Institute of Technology , Matsugasaki, Kyoto, Japan.
Oligonucleotides. 2011 Mar-Apr;21(2):115-21. doi: 10.1089/oli.2010.0277.
"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.
“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(-),由于其侵袭性肿瘤表型,通常与不良预后相关。近年来,乳腺癌患者数量显著增加,但治疗TN乳腺癌的可用药物却很少。迫切需要开发针对TN乳腺癌的新型药物。在本研究中,我们聚焦于特殊富含AT序列结合蛋白1(SATB1)的功能,将其作为治疗TN乳腺癌的靶分子。通过募集染色质重塑酶和转录因子,SATB1调节1000多个与细胞生长和易位相关的基因的表达。我们合成了一种针对SATB1的诱饵DNA,其中包含SATB1的识别序列。我们检测了诱饵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抑制了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,对于MCF7细胞(SATB1阴性乳腺癌细胞系),SATB1诱饵DNA未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,用于治疗TN乳腺癌。