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(American Journal of Pathology. 1999;155:1105-1113.)
© 1999 American Society for Investigative Pathology

Regular Articles

Overexpression of Pterin-4a-carbinolamine Dehydratase/Dimerization Cofactor of Hepatocyte Nuclear Factor 1 in Human Colon Cancer

Rally Eskinazi^*, Beat Thöny^§, Michal Svoboda^*, Patrick Robberecht^*, Donald Dassesse, Claus W. Heizmann^§, Jean-Luc Van Laethem^* and Anne Resibois

From the Laboratoire de Chimie Biologique et de la Nutrition,^*
Faculté de Médecine, the Département de Gastroentérologie,
Hôpital Erasme, and the Laboratoire d'Histologie,
Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium; and the Division of Clinical Chemistry and Biochemistry,^§
Department of Pediatrics, University of Zürich, Zürich, Switzerland

Pterin-4a-carbinolamine dehydratase (PCD) is a bifunctional protein also known as DCoH (dimerization co-factor of hepatocyte nuclear factor 1 (HNF1)). PCD/DCoH modulates the DNA binding specificity of HNF1, thus acting on its transcriptional activity. In addition, it participates in the recycling of tetrahydrobiopterin (BH₄), an essential cofactor of several metabolic reactions. We investigated colorectal tumors and colorectal tumor cell lines as compared to normal colon samples in search of a potential differential expression of PCD/DCoH. Immunohistochemistry was conducted on 20 human colorectal tumors and 20 normal samples using a specific polyclonal antibody. Immunoblotting and RT-PCR analysis for PCD/DCoH and HNF1 were also performed on both human tissues and CACO-2 and HT-29 cell lines. All of the 20 tumors and both colon cancer cell lines presented a strong and widespread immunoreactivity for PCD/DCoH, contrasting with the absence of expression in the normal epithelia. We thus report the massive overexpression of PCD/DCoH in colon tumors, which is in striking contrast with the absence of staining in normal counterparts. The sharp contrast in the expression of a modulator of transcriptional activity between tumoral and normal cells may have a physiopathological role. PCD/DCoH could potentially be a new marker of malignant colon cells in vivo.

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