Graham R A, Morris J R, Cohen E P, Taylor-Papadimitriou J
Imperial Cancer Research Fund, Breast Cancer Biology Group, Guys Hospital, London, United Kingdom.
Int J Cancer. 2001 May 1;92(3):382-7. doi: 10.1002/ijc.1192.
In this study we examined the regulation of expression of the human MUC1 gene in vivo, by developing MUC1 transgenic mice. The data showed that epithelial-specific expression of MUC1 can be directed by just 1.4 kb of 5' flanking sequence using MUC1 cDNA as a reporter gene in vivo. Furthermore, high levels of MUC1 expression were seen in the lactating mammary gland and in spontaneous mammary tumors generated by crossing the MUC1 transgenics with mice transgenic for the polyoma middle T oncogene under the control of the mouse mammary tumor virus promoter. This pattern of expression in epithelial tissues is comparable to the expression of MUC1 in humans and also to the expression pattern in another transgenic mouse line developed with a 10.6-kb genomic MUC1 fragment. This study confirmed that MUC1 is a compact gene and demonstrated that the 1.4-kb 5' sequence not only directs epithelial-specific expression of MUC1 in vivo but also contains the elements governing the up-regulation observed during lactation and in malignancy.
在本研究中，我们通过培育MUC1转基因小鼠，研究了人MUC1基因在体内的表达调控。数据表明，在体内以MUC1 cDNA作为报告基因时，仅1.4 kb的5'侧翼序列就能指导MUC1的上皮特异性表达。此外，在泌乳期乳腺以及通过将MUC1转基因小鼠与在小鼠乳腺肿瘤病毒启动子控制下的多瘤中间T癌基因转基因小鼠杂交产生的自发性乳腺肿瘤中，观察到了高水平的MUC1表达。上皮组织中的这种表达模式与人类MUC1的表达以及另一个用10.6 kb基因组MUC1片段构建的转基因小鼠品系中的表达模式相当。本研究证实MUC1是一个紧密型基因，并表明1.4 kb的5'序列不仅在体内指导MUC1的上皮特异性表达，还包含在泌乳期和恶性肿瘤中观察到的上调调控元件。
