Lu Ming, Sartippour Maryam R, Zhang Liping, Norris Andrew J, Brooks Mai N
University of California, Los Angeles School of Medicine, Department of Surgery, Division of Oncology, Los Angeles, California, USA.
Cancer Biol Ther. 2007 Jun;6(6):936-41. doi: 10.4161/cbt.6.6.4189. Epub 2007 Mar 26.
EG-1 is a gene product that is significantly elevated in human breast cancer tissues. Previously, we have shown that EG-1 overexpression stimulates cellular proliferation both in vitro and in vivo. Here, we ask whether this molecule can be targeted for experimental therapeutic purpose. siRNA lentivirus and polyclonal antibodies were designed to suppress EG-1 expression. These agents were then used in cell culture proliferation assays and breast tumor xenograft models. Serum and urine from breast cancer patients were also analyzed for the presence of EG-1 peptide. We report here for the first time that endogenous EG-1 can be targeted to inhibit breast tumor growth. This inhibition, whether delivered via siRNA lentivirus or polyclonal antibody, resulted in decreased cellular proliferation in culture and smaller xenografts in mice. The effects were shown in both ER (estrogen receptor)-positive human breast cancer MCF-7 cells, as well as in ER-negative MDA-MB-231 cells. Furthermore, we detected soluble EG-1 in serum and urine of breast cancer patients. These observations demonstrate that EG-1 is relevant to human breast cancer, and is a molecular target worthy of translational efforts into effective breast cancer therapy.
EG-1是一种在人类乳腺癌组织中显著升高的基因产物。此前，我们已经表明EG-1的过表达在体外和体内均能刺激细胞增殖。在此，我们探讨该分子是否可作为实验性治疗靶点。设计了siRNA慢病毒和多克隆抗体以抑制EG-1表达。然后将这些试剂用于细胞培养增殖试验和乳腺肿瘤异种移植模型。还分析了乳腺癌患者的血清和尿液中是否存在EG-1肽。我们首次在此报告，内源性EG-1可作为靶点来抑制乳腺肿瘤生长。这种抑制作用，无论是通过siRNA慢病毒还是多克隆抗体介导，均导致培养中的细胞增殖减少以及小鼠体内异种移植瘤变小。在雌激素受体（ER）阳性的人乳腺癌MCF-7细胞以及ER阴性的MDA-MB-231细胞中均显示出这种效果。此外，我们在乳腺癌患者的血清和尿液中检测到了可溶性EG-1。这些观察结果表明，EG-1与人类乳腺癌相关，是一个值得转化为有效乳腺癌治疗方法的分子靶点。
