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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*{dagger}, Beat Thöny§, Michal Svoboda*, Patrick Robberecht*, Donald Dassesse{ddagger}, Claus W. Heizmann§, Jean-Luc Van Laethem*{dagger} and Anne Resibois{ddagger}

From the Laboratoire de Chimie Biologique et de la Nutrition,*
Faculté de Médecine, the Département de Gastroentérologie,{dagger}
Hôpital Erasme, and the Laboratoire d'Histologie,{ddagger}
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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