Regulation of a novel colon specific retinol dehydrogenase...

A - Human Necessities – 61 – K

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A61K 31/07 (2006.01) A61K 38/17 (2006.01) C07K 14/47 (2006.01)

Patent

CA 2481239

New methods of screening for compounds for treating colon cancer are described. Using microarray expression profiling, molecular evidence was obtained supporting lack of differentiation as the mechanism for development of colon polyps and tumors. An absence of retinoic acid (RA) response genes from neoplastic tissue colon tissues was observed. The absence of RA response genes was paralleled by the lack of expression of retinol dehydrogenase 5 and a novel retinol dehydrogenase homolog, RDHL. RDHL expression is highly restricted to normal colon and the colon specific transcription factors, cdx1 and cdx2 can regulate RDHL. Additionally, re-introduction of APC leads to re- expression of RDHL.

L'invention concerne de nouveaux procédés de détection de composés pour traiter le cancer du colon. A l'aide d'une technique de profilage d'expression de microréseaux, on a mis en évidence, sur le plan moléculaire, que l'absence de différentiation constituait le mécanisme de développement des polypes du colon et des tumeurs. Une absence de gènes de réponse à l'acide rétinoïque des tissus du colon néoplastques a été observée. On a établi un parallèle entre l'absence de ces gènes et le manque d'expression de la rétinol déshydrogénase 5 et d'un nouvel homologue de la rétinol déshydrogénase, RDHL. L'expression de RDHL est essentiellement restreinte au colon normal, et les facteurs de transcription spécifiques au colon, cdx1 et cdx2 peuvent réguler RDHL. En outre, une nouvelle introduction du gène APC se traduit par une nouvelle expression de RDHL.

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