Volume 120, Issue 3 pp. 477-483
Carcinogenesis

Progression of tumors arising from large ACF is associated with the MUC5AC expression during rat colon MNNG carcinogenis

Nicole Maurin

Nicole Maurin

Laboratoire d'Histologie, GHU Pierre et Marie Curie, Hôpital St-Antoine, Paris, France

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Marie-Elisabeth Forgue-Lafitte

Marie-Elisabeth Forgue-Lafitte

U-673 INSERM, Hôpital St-Antoine, Paris, France

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Pierre Levy

Pierre Levy

Departement de Santé Publique, Hôpital Tenon–APHP–Inserm, France

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Amazia Zimber

Amazia Zimber

Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot, Israel

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Jacques Bara

Corresponding Author

Jacques Bara

U-673 INSERM, Hôpital St-Antoine, Paris, France

Fax: +33-1-44-74-93-18.

U-673 INSERM, Hôpital St-Antoine–184, rue duFaubourg St-Antoine, 75012 Paris, FranceSearch for more papers by this author
First published: 25 October 2006
Citations: 13

Abstract

Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomas, precursors of colon cancer. The gastric M1/MUC5AC mucin has also been described as an early marker of colon carcinogenesis in the human and in the rat. To study changes in mucin expression associated with the genesis of tumors, Wistar rats were treated by intrarectal instillations of MNNG, twice a week for 2 weeks, and were sacrificed 10 (n = 20), 14 (n = 20), 22 (n = 20), 30 (n = 10) and 66 (n = 16) weeks after the beginning of the treatment. In the treated rats, the MUC5AC mucin was mainly expressed in ACF compared with the histologically normal mucosae, which showed few isolated MUC5AC-positive normal crypts. During carcinogenesis, the percentage of large ACF [≥≥10 aberrant crypts] increased and the number of MUC5AC-positive (NCs) decreased. At Week 30, small tumors were observed arising from large ACF, both types of lesions expressing MUC5AC. At Week 66, large tumors showed remnants of MUC5AC-positive ACF in their adjacent mucosae. This observation suggests that the expression of MUC5AC is associated with the ACF/adenoma sequence and supports the notion of large ACF as precursors of adenomas/adenocarcinomas. Moreover, the expression of MUC5AC in the transitional mucosa adjacent to both rat and human colon tumors suggests that some human tumors could arise from large ACF, and reinforces the concept of the premalignant potential of these lesions. © 2006 Wiley-Liss, Inc.

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