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Volume 39, Issue 10, Pages 1420-1430 (October 2008)


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In colon carcinogenesis, the cytoskeletal protein gelsolin is down-regulated during the transition from adenoma to carcinoma

Fabien Gay, PhD studentabc, Yann Estornes, PhDabc, Jean-Christophe Saurin, MD, PhDabc, Marie-Odile Joly-Pharaboz, MDabcd, Evelyne Friederich, PhDe, Jean-Yves Scoazec, MD, PhDabcd, Jacques Abello, PhDabcCorresponding Author Informationemail address

Received 9 November 2007; received in revised form 7 February 2008; accepted 25 February 2008. published online 25 July 2008.

Summary 

The actin-binding protein gelsolin is involved in cell motility via the regulation of actin cytoskeleton, and its expression is modified in several human cancers. However, the potential implication of this protein in colorectal carcinogenesis is debated. By using immunohistochemistry, we studied gelsolin expression in 69 cases of colon adenocarcinomas and in 72 lesions representative of the different stages of colonic tumorigenesis. In addition, we performed Northern blot analysis of gelsolin messenger RNA in 12 paired samples of human colon cancer and normal corresponding mucosa. Gelsolin protein and messenger RNA expressions were severely down-regulated in all adenocarcinomas tested. Moreover, gelsolin protein was down-regulated in a large proportion of high-grade adenomas (14/16) before the acquisition of invasive properties but in only a small proportion of low grade adenomas and serrated adenomas (2/30) and in none of the 9 cases of nonneoplastic hyperplastic polyps tested. Our results therefore demonstrate that gelsolin down-regulation is an early and almost constant event in colon carcinogenesis and is associated with the transition from adenoma to carcinoma.

a Inserm, U865, Lyon, F-69372, France; Inserm, IFR62, Lyon, F-69372, France

b Université de Lyon, Lyon, F-69003, France

c Université de Lyon 1, F-69372 Villeurbanne, France

d Hospices Civils de Lyon, Hôpital Edouard Herriot, Service Central d’Anatomie et Cytologie Pathologiques, F-69437 Lyon, France

e Department of Life Sciences, University of Luxembourg, L-1511, Luxembourg, Luxembourg

Corresponding Author InformationCorresponding author.

 This work was supported by grants from the Ligue Nationale contre le Cancer, Comité du Rhône (Lyon, France) and from the Cancéropôle Lyon-Auvergne-Rhône-Alpes (CLARA; Lyon, France).

PII: S0046-8177(08)00153-6

doi:10.1016/j.humpath.2008.02.020


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