Li Xiaojing, Wang Li, Nunes David P, Troxler Robert F, Offner Gwynneth D
Department of Medicine, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Cancer Biol Ther. 2005 Sep;4(9):968-73. doi: 10.4161/cbt.4.9.1913. Epub 2005 Sep 13.
The transmembrane mucin, MUC1, is overexpressed on many human carcinoma cells, increasing their metastatic potential through decreased cell-cell and cell-matrix adhesion. These cellular changes are mediated both through the altered physical properties of the mucin itself and through the role of the MUC1 cytoplasmic domain as a signaling molecule. The epidermal growth factor receptor (EGFR) is also overexpressed in many cancers and both it and MUC1 constitute important therapeutic targets. In the present study, expression of MUC1 was downregulated by treatment of KB carcinoma cells with a MUC1 small interfering RNA resulting in an inhibition of cell proliferation and colony formation and an increase in cell-cell aggregation. Surprisingly, suppression of MUC1 also inhibited expression of EGFR at both the mRNA and protein levels whereas the reciprocal effect was not observed. These results demonstrate a role for MUC1 in the regulation of EGFR expression and suggest that MUC1 gene silencing may represent a novel therapeutic approach in the treatment of a variety of human cancers.
跨膜黏蛋白MUC1在许多人类癌细胞上过度表达，通过降低细胞间和细胞与基质的黏附力来增加其转移潜能。这些细胞变化既通过黏蛋白自身物理性质的改变介导，也通过MUC1细胞质结构域作为信号分子的作用介导。表皮生长因子受体（EGFR）在许多癌症中也过度表达，它和MUC1都是重要的治疗靶点。在本研究中，用MUC1小干扰RNA处理KB癌细胞可下调MUC1的表达，导致细胞增殖和集落形成受到抑制，细胞间聚集增加。令人惊讶的是，抑制MUC1在mRNA和蛋白质水平上也抑制了EGFR的表达，而未观察到相反的作用。这些结果证明了MUC1在EGFR表达调控中的作用，并表明MUC1基因沉默可能代表了一种治疗多种人类癌症的新方法。
