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Gut cancers differentiate without CDX2

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Cell differentiation in intestinal adenomas and carcinomas has been shown to be regulated independently of a transcription factor important in maintaining gut epithelium. A molecular study has shown a new in vitro model of premalignant adenoma cell lines to be suitable for understanding CDX expression and tumour development and has refuted a previous suggestion that transcription factor CDX2 plays a part in differentiation.

CDX1 and CDX2 were expressed more in the adenoma cell lines compared with two carcinoma cell lines. When the cells were induced to stop growing and instead differentiate by treatment with sodium butyrate, a natural product of the intestinal microflora, expression of CDX1 and CDX2 were unaffected in two selected adenoma cell lines but rose slightly in the carcinoma cell lines. Inducing differentiation by allowing the cell lines to grow to confluence, before assaying for CDX1 and CDX2, gave similar results. However, the level of expression attained fell far short of expression in the adenoma cell lines

CDX1 and CDX2 were assayed by western blotting in six premalignant adenoma cell lines with high expression of these transcription factors and two carcinoma cell lines with lower CDX expression.

CDX1 and CDX2 transcription factors, specified by Cdx genes, are reduced in the development of colorectal cancers. CDX2, at least, is important in transcribing genes for differentiation in intestinal epithelium. Existing evidence is based on in vitro studies with cell lines from colorectal cancers whereas this new evidence comes from adenoma cell lines, which are closer to “normal” colonic epithelium.

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