Howlin J, McBryan J, Napoletano S, Lambe T, McArdle E, Shioda T, Martin F
UCD Conway Institute and School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
Oncogene. 2006 Mar 9;25(10):1532-42. doi: 10.1038/sj.onc.1209183.
Expression microarray analysis identified CITED1 among a group of genes specifically upregulated in the pubertal mouse mammary gland. At puberty, CITED1 localizes to the luminal epithelial cell population of the mammary ducts and the body cells of the terminal end buds. Generation of CITED1 gene knockout mice showed that homozygous null mutants exhibit retarded mammary ductal growth at puberty and, in addition, dilated ductal structures with a lack of spatial restriction of the subtending branches. Analysis of CITED1 homozygous null and heterozygous null mammary gland gene expression using microarrays suggested that the mammary-specific phenotype seen in the homozygous null females is due to a disturbance in the transcription of a number of key mediators of pubertal ductal morphogenesis. These include estrogen and TGFbeta responsive genes, such as the EGFR/ErbB2 ligand, amphiregulin, whose transcription we suggest is directly or indirectly regulated by CITED1.
表达微阵列分析在一组于青春期小鼠乳腺中特异性上调的基因中鉴定出了CITED1。在青春期，CITED1定位于乳腺导管的腔上皮细胞群体以及末端芽的体细胞。CITED1基因敲除小鼠的产生表明，纯合无效突变体在青春期表现出乳腺导管生长迟缓，此外，导管结构扩张，其分支缺乏空间限制。使用微阵列对CITED1纯合无效和杂合无效乳腺基因表达进行分析表明，在纯合无效雌性小鼠中观察到的乳腺特异性表型是由于青春期导管形态发生的一些关键介质转录受到干扰所致。这些介质包括雌激素和TGFβ反应基因，如EGFR/ErbB2配体双调蛋白，我们认为其转录直接或间接受CITED1调控。
