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Journal of Histochemistry and Cytochemistry, Vol. 47, 1315-1322, October 1999, Copyright © 1999, The Histochemical Society, Inc.

ARTICLE

High Expression of MDM2 Protein and Low Rate of p21WAF1/CIP1 Expression in SCID Mice Epstein Barr Virus-induced Lymphoproliferation

Saïd El Mansouria,e, Antoine Martina,b, Anne Mercadiera,b, Corrine Capouladed, Vincent Maréchalc, Joëlle Wielsd, Jean Feuillarda, and Martine Raphaëla
a Service d'Hématologie Biologique, EA 1625, and Service d'Anatomie Pathologique, Hôpital Avicenne, UFR SMBH Léonard de Vinci, Université Paris XIII, Bobigny
b Centre de Transfusion Sanguine, Hôpital Pitié-Salpêtrière
c Service de Microbiologie, Hôpital Rothschild, Paris
d Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Institut Gustave Roussy, Villejuif, France
e Laboratoire de Phytochimie et de Pharmacognosie, Faculté des Sciences, Université Mohamed Premier, Oujda, Morocco

Correspondence to: Antoine Martin, Service d'Hématologie Biologique, Hôpital Avicenne, 125 Route de Stalingrad, 93009 Bobigny Cedex, France.

To study the prevalence of p53 inactivation and MDM2/p21WAFI/CIP1 expression in severe combined immunodeficient (SCID) mice Epstein-Barr virus (EBV)-induced lymphoproliferation, 19 samples obtained after IP injection of peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors or lymphoblastoid cell lines (LCL) were analyzed. In all samples tested, overexpression of Ki-67 antigen was shown by immunohistochemistry, indicating a high proliferative index of SCID mice EBV-induced lymphoproliferation. P53 mutations were screened by functional assay in yeast in 14 samples. With this test, a p53-inactivating mutation was found in only one case; the remaining cases exhibited a wild-type p53 pattern. However, an accumulation of p53 protein was detected by immunohistochemistry in six of 19 samples. P21 expression was found in seven of 19 samples but was not correlated with the rate of p53 protein in tumors. In contrast, high levels of nuclear accumulation of MDM2 were found in all samples by immunohistochemistry. These results suggest that a high Ki-67 proliferative index in SCID mice EBV-induced lymphoproliferation is not due to the inactivation of p53 by mutation, but could be associated with an overexpression of MDM2, which would act by a p53-independent mechanism.

(J Histochem Cytochem 47:1315–1321, 1999)

Key Words: p53, MDM2, p21WAFI/CIP1, SCID mice, EBV, lymphoproliferation, human


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