Sun Fuqiang, Lu Xiaoming, Li Hang, Peng Zhao, Wu Ke, Wang Guobin, Tong Qiang
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Oncol Lett. 2012 Jul;4(1):156-162. doi: 10.3892/ol.2012.681. Epub 2012 Apr 17.
Special AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as a global chromatin organizer to regulate gene expression. Recent studies have suggested an oncogenic role of SATB1 in breast cancer. However, the role of SATB1 in gastric cancer, especially in regulating the malignant phenotypes, including multidrug resistance (MDR) and metastasis, remains poorly understood. In this study, the aggressive human gastric cancer cell line SGC7901 and its corresponding MDR variant SGC7901/VCR cells were used as a model. SATB1 expression was examined by RT-PCR and western blot analysis. Results showed that SATB1 was upregulated in SGC7901/VCR cells. An in vitro drug sensitivity assay demonstrated a positive correlation between SATB1 expression levels and drug resistance. Gain and loss of SATB1 function experiments further demonstrated that SATB1 contributes to MDR by inhibiting the accumulation of vincristine (VCR) in gastric cancer cells and protecting the cells from VCR-induced apoptosis. In addition, SATB1 may promote the invasion of gastric cancer cells. The present study provides a novel insight into the oncogenic role of SATB1 in gastric cancer, suggesting that SATB1 is a promising target for the therapy of drug-resistant and invasive gastric cancer.
富含AT序列结合蛋白1（SATB1）是一种核因子，作为一种全局染色质组织者发挥作用，以调节基因表达。最近的研究表明SATB1在乳腺癌中具有致癌作用。然而，SATB1在胃癌中的作用，尤其是在调节包括多药耐药（MDR）和转移在内的恶性表型方面，仍知之甚少。在本研究中，侵袭性人胃癌细胞系SGC7901及其相应的MDR变体SGC7901/VCR细胞被用作模型。通过RT-PCR和蛋白质印迹分析检测SATB1的表达。结果显示，SATB1在SGC7901/VCR细胞中上调。体外药物敏感性试验表明SATB1表达水平与耐药性呈正相关。SATB1功能的获得和缺失实验进一步证明，SATB1通过抑制长春新碱（VCR）在胃癌细胞中的积累并保护细胞免受VCR诱导的凋亡，从而导致MDR。此外，SATB1可能促进胃癌细胞的侵袭。本研究为SATB1在胃癌中的致癌作用提供了新的见解，表明SATB1是耐药性和侵袭性胃癌治疗的一个有前景的靶点。
