This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chaigne-Delalande, B. Articles by Génot, E. Search for Related Content PubMed PubMed Citation Articles by Chaigne-Delalande, B. Articles by Génot, E.

(American Journal of Pathology. 2006;168:562-573.)
© 2006 American Society for Investigative Pathology

RhoGTPases and p53 Are Involved in the Morphological Appearance and Interferon- Response of Hairy Cells

Benjamin Chaigne-Delalande^*, Lynda Deuve^*, Edith Reuzeau^*, Caroline Basoni^*, David Lafarge^*, Christine Varon^*, Florence Tatin^*, Guerric Anies^*, Richard Garand, Ijsbrand Kramer^* and Elisabeth Génot^*

From Unité 441,^* Institut National de la Recherché Médicale, University Victor Segalen Bordeaux, Bordeaux, and the European Institute of Chemistry and Biology, University of Bordeaux I, Talence; and the Laboratoire d’Hématologie, Institut de Biologie, Centre Hospitalier Universitaire, Nantes, France

Hairy cell leukemia is an uncommon B-cell lymphoproliferative disease of unknown etiology in which tumor cells display characteristic microfilamentous membrane projections. Another striking feature of the disease is its exquisite sensitivity to interferon (IFN)-. So far, none of the known IFN- regulatory properties have explained IFN- responsiveness nor have they taken into account the morphological characteristics of hairy cells. IFN- profoundly alters cytoskeletal organization of hairy cells and causes reversion of the hairy appearance into a rounded morphology. Because cytoskeletal rearrangements are controlled by the Rho family of GTPases, we investigated the GTPase activation status in hairy cells and their regulation by IFN-. Using immunolocalization techniques and biochemical assays, we demonstrate that hairy cells display high levels of active Cdc42 and Rac1 and that IFN- down-regulates these activities. In sharp contrast, RhoA activity was low in hairy cells but was increased by IFN- treatment. Finally, IFN--mediated morphological changes also implicated a p53-induced response. These observations shed light on the mechanism of action of IFN- in hairy cell leukemia and are of poten-tial relevance for the therapeutical applications of this cytokine.

This article has been cited by other articles:

				C. Munoz-Fontela, M. A. Garcia, M. Collado, L. Marcos-Villar, P. Gallego, M. Esteban, and C. Rivas Control of virus infection by tumour suppressors Carcinogenesis, June 1, 2007; 28(6): 1140 - 1144. [Abstract] [Full Text] [PDF]