CDX1 expression is reduced in colorectal carcinoma and is associated with promoter hypermethylation

The Journal of Pathology
Emanuela PilozziLuigi Ruco

Abstract

The CDX1 homeobox gene encodes a transcription factor specifically expressed in normal intestinal and colonic epithelia, and CDX1 gene expression is affected during colorectal tumour progression. In this study, real-time quantitative RT-PCR was used to investigate CDX1 expression in 26 colorectal carcinomas. Reduced expression of CDX1 was observed in 19 of 26 colon carcinomas compared to matched normal colonic mucosa: the decrease in CDX1 expression ranged between 0.10 and 0.79 (21-90% decrease; mean 64.75% +/-22; p = 0.001). Mutation and loss of heterozygosity (LOH) analyses were then used to determine if reduced CDX1 expression was due to genetic alteration. No CDX1 gene mutations, but two known polymorphisms in exon 1, were observed. LOH was observed in 33% of the tumours investigated but this was not related to CDX1 expression. Since aberrant promoter methylation is a well-known mechanism that participates in gene silencing, the methylation status of the CDX1 5' CpG island promoter was also investigated. PCR amplification of bisulphite-treated DNA followed by cloning was performed in 7 carcinomas that showed low expression of CDX1 and in 1 colonic carcinoma without reduced expression. Promoter hypermethylation occurred in c...Continue Reading

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Citations

Aug 6, 2005·Journal of Gastroenterology·Tatsuya AndoKazuyuki Suzuki
Oct 3, 2009·Digestive Diseases and Sciences·Xiaobing ChenYinchun Jin
Jan 31, 2008·Neoplasia : an International Journal for Oncology Research·Mary Ann S CrisseyJohn P Lynch
Dec 13, 2006·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Yuan ChenIver Petersen
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Jan 28, 2019·Pathology Oncology Research : POR·Ali Akbar SamadaniHaleh Akhavan-Niaki
Feb 3, 2021·Genes·Yalun ZhuDavid Lohnes

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