HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Aguiló, J. I. Articles by Anel, A. Search for Related Content PubMed PubMed Citation Articles by Aguiló, J. I. Articles by Anel, A.

Protein Kinase C- Is Required for NK Cell Activation and In Vivo Control of Tumor Progression¹

Juan I. Aguiló^*, Johan Garaude, Julián Pardo^*,, Martín Villalba and Alberto Anel^2,*

^* Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain; Institute of Genetics of Montpellier, National Center of Scientific Research, Mixed Unit of Research 5535, Montpellier, France, and Aragón Research and Devlopment Foundation, Government of Aragón, Zaragoza, Spain

Protein kinase C- (PKC) was initially isolated as an important PKC isoform expressed in T cells, although its expression is not restricted to these cells. Despite the central function of PKC in several immune responses, its role in the antitumor response against MHC class I (MHC-I)-negative cells has not been investigated. This is an important issue because most tumor cells growing in vivo down-regulate MHC-I expression to escape the CTL-mediated response. In the present work, we show that in vivo development of a MHC-I-deficient tumor (RMA-S) is much favored in PKC^–/– mice compared with wild-type mice. This is associated with a reduced recruitment of NK cells to the site of tumor development and a reduced activation status of recruited NK cells. This correlates with a reduced ex vivo and in vivo cytotoxic potential of NK cells isolated from PKC^–/– mice treated with polyinosinic:polycytidylic acid. Consistently, polinosinic:cytidilic acid treatment induces PKC expression and activation of its enzymatic activity in NK cells in an indirect manner. These observations underline the relevance of PKC as a key molecule in NK cell-mediated antitumor immune surveillance.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant SAF2007-65144 (to A.A.) from the Ministerio de Ciencia e Innovación/Fondo Social Europeo (Spain) and by the Institut National du Cancer/Cancéropôle Grand Sud-Ouest (to M.V.) (France). J.I.A. had a Formación de Personal Investigador Fellowship associated with Grant SAF2004-03058 from the Ministerio de Educación y Ciencia/Fondo Social Europeo. J.P. is supported by Fundación Aragón I+D (Gobierno de Aragón, Spain).

² Address correspondence and reprint requests to Dr. Alberto Anel, Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, University of Zaragoza, Zaragoza, 50009, Spain. E-mail address: anel{at}posta.unizar.es

³ Abbreviations used in this paper: PKC, protein kinase C-; MHC-I, MHC class I; FasL, Fas ligand; PEC, peritoneal exudate cell; poly(I:C), polyinosinic:polycytidylic acid; wt/WT, wild type; KO/ko, knockout.