Domon-Dell Claire, Schneider Anne, Moucadel Virginie, Guerin Eric, Guenot Dominique, Aguillon Sarah, Duluc Isabelle, Martin Elisabeth, Iovanna Juan, Launay Jean-François, Duclos Bernard, Chenard Marie-Pierre, Meyer Christian, Oudet Pierre, Kedinger Michèle, Gaub Marie-Pierre, Freund Jean-Noël
Institut National de la Santé et de la Recherche Médicale, Unité 381, 3 Avenue Molière, 67200 Strasbourg, France.
Oncogene. 2003 Sep 11;22(39):7913-21. doi: 10.1038/sj.onc.1206756.
The Cdx1 homeobox gene encodes an intestine-specific transcription factor with a pro-oncogenic function in vitro. Here we have analysed the pattern of Cdx1 in human colon cancer progression. Cdx1 expression remains at a high level in the majority of the polyps and it is even overexpressed in more than one-third of the specimens, consistent with the fact that the gene is an intestine-specific target of oncogenic pathways. However, Cdx1 decreases in one-fifth of the polyps, which is reminiscent of the loss of expression previously reported in the majority of carcinomas. Allelic imbalance analysis demonstrates that the Cdx1 locus located on chromosome 5q is a major site of genomic rearrangement in colorectal cancers, and that the frequency of the rearrangements increases during polyps to carcinoma progression. Allelic imbalance at the Cdx1 locus occurs in relation to, although not invariably in association with, the rearrangements at the APC locus on the same chromosomal arm. Xenografts of primary human colon carcinomas indicate that the level of Cdx1 mRNA correlates with the intensity of allelic imbalance. Together, these data show that Cdx1 exhibits a complex pattern during colorectal cancer progression. Given that Cdx1 has a pro-oncogenic function in vitro, the maintenance of a high level of expression in polyps, and even its overexpression in one-third of the specimens, suggest that this homeobox gene may be an important factor in the process toward malignant transformation during the first steps of tumorigenesis.
Cdx1同源框基因编码一种在体外具有促癌功能的肠道特异性转录因子。在此，我们分析了Cdx1在人类结肠癌进展过程中的模式。Cdx1在大多数息肉中保持高水平表达，甚至在超过三分之一的标本中过表达，这与该基因是致癌途径的肠道特异性靶点这一事实相符。然而，五分之一的息肉中Cdx1表达下降，这让人想起先前在大多数癌中报道的表达缺失。等位基因失衡分析表明，位于5号染色体q臂上的Cdx1基因座是结直肠癌基因组重排的主要位点，并且在息肉向癌进展过程中重排频率增加。Cdx1基因座的等位基因失衡与同一染色体臂上APC基因座的重排有关，尽管并非总是相关。原发性人类结肠癌的异种移植表明，Cdx1 mRNA水平与等位基因失衡强度相关。总之，这些数据表明Cdx1在结直肠癌进展过程中呈现出复杂的模式。鉴于Cdx1在体外具有促癌功能，息肉中高水平表达的维持，甚至在三分之一的标本中过表达，表明这个同源框基因可能是肿瘤发生第一步中向恶性转化过程中的一个重要因素。
