Intervirology
Original Paper
Modulatory Effects of Human Cytomegalovirus Infection on Malignant Properties of Cancer CellsCinatl Jr J.a · Cinatl J.a,b · Vogel J.-U.a,b · Rabenau H.a · Kornhuber B.b · Doerr H.W.aa Institute of Medical Virology, University Clinics of Frankfurt/Main, and b Centre of Pediatrics, Department of Haematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany
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Article / Publication Details
Received: March 06, 1996
Accepted: September 16, 1996
Published online: July 30, 2008
Issue release date: 1996
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)
For additional information: https://www.karger.com/INT
Abstract
Although there is no definitive evidence of the association of human cytomegalovirus (HCMV) infection with human cancers, the oncogenic potential of HCMV has been well established by in vitro studies demonstrating the ability of UV-irradiated or infectious virus to transform a variety of cells. After prolonged passaging the transformed cell type was maintained while HCMV DNA sequences were no more detectable. Three morphological transforming regions (mtr) of HCMV have been identified. The effects of HCMV on cellular functions which may be associated with the malignant phenotype include the expression of oncogenes and transcriptional activation of growth factors and interleukin synthesis. In infected cells, HCMV induces cytoskeletal alterations and changes in expression of cell surface receptors for extracellular matrix proteins which could result in increased motility and dissemination of cancer cells. Several human neuroblastoma cell lines undergo maturation in different neural crest derived cell types upon treatment with oncogenic potential agents, i. e. retinoic acid. The persistent HCMV infection of neuroblastoma cells (>1 year) is accompanied by the increased expression of oncoproteins (i.e. N-myc) and decreased expression of tyrosine hydroxylase and dopamine-β-hydroxylase. The activation of the cellular metabolism is due to HCMV binding to cellular receptors (prior to virus gene expression) and to the activity of HCMV immediate early (IE) gene products. IE proteins act directly as transcriptional activators or their activity is mediated by a variety of cellular transcription factors. HCMV infection may result in activation of promoters of cellular genes coding for cytokines, replication enzymes, protooncogenes and viral promoters. Recently it has been demonstrated that HCMV IE proteins block apoptosis probably by suppressing the ability of the antioncogene p53 to activate a reporter gene. The interactions of HCMV with tumor suppressor proteins such as p53 or retinoblastoma (pRb) susceptibility protein are reminiscent of those mediated by the oncoproteins of DNA tumor viruses. The acquisition of a fully malignant phenotype by normal cells is thought to require several mutations in a number of cellular genes. In this connection, HCMV may play the role of a nonobligate either direct or indirect cofactor for tumor genesis, e.g. by blocking apoptosis, which may be an essential requirement for tumor progression. Due to the stimulation of growth factors and/or inhibition of antioncogenes by its gene products, HCMV may modulate the malignant potential of tumor cells.
© 1996 S. Karger AG, Basel
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Article / Publication Details
Received: March 06, 1996
Accepted: September 16, 1996
Published online: July 30, 2008
Issue release date: 1996
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)
For additional information: https://www.karger.com/INT
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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