Suppression of MUC1 synthesis downregulates expression of the epidermal growth factor receptor
Suppression of MUC1 synthesis downregulates expression of the epidermal growth factor receptor
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DOI：
10.4161/cbt.4.9.1913
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发表时间：
2005-09-01
影响因子：
3.6
通讯作者：
Offner, GD
中科院分区：
文献类型：
--
作者：
Li, XJ;Wang, L;Offner, GD
跨膜粘蛋白MUC1在许多人类癌细胞上过度表达，通过减少细胞与细胞和细胞与基质的黏附而增加其转移潜能。这些细胞变化既是通过改变粘蛋白本身的物理性质，也通过MUC1细胞质结构域作为信号分子的作用来调节的。表皮生长因子受体(EGFR)在许多癌症中也过表达，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癌细胞后，MUC1的表达下调，从而抑制了细胞的增殖和集落形成，增加了细胞间的聚集性。令人惊讶的是，抑制MUC1也在mRNA和蛋白水平上抑制了EGFR的表达，但没有观察到交互作用。这些结果证明了MUC1在调节EGFR表达中的作用，并提示MUC1基因沉默可能是治疗多种人类癌症的一种新的治疗方法。
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.