~ Advances in CANCER RESEARCH Volume 68 This Page Intentionally Left Blank Advances in CANCER RESEARCH Volume 68 Edited by George F. Vande Woude ABL-Basic Research Program National Cancer Institute Frederick Cancer Research and Development Center Frederick, Maryland George Klein Microbiology and Tumor Biology Center (MTC) Karolinska lnstitutet Stockholm, Sweden ACADEMIC PRESS San Diego New York Boston London Sydney Tokyo Toronto This book is printed on acid-free paper. @ Copyright 0 1996 by ACADEMIC PRESS, INC. All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Academic Press, Inc. A Division of Harcourt Brace &. Company 525 B Street, Suite 1900, San Diego, California92101-4495 United Kingdom Edition published by Academic Press Limited 24-28 Oval Road, London NW I 7DX International Standard Serial Number: 0065-230X International Standard Book Number: 0- 12-006668-8 PRINTED IN THE UNITED STATES OF AMERICA 96 97 98 99 00 01 BB 9 8 7 6 5 4 3 2 1 Contents Contributors to Volume 68 ix FOUNDATIONS IN CANCER RESEARCH Viruses in Human Tumors-Reminiscences and Perspectives Harald zur H a u s e n 1. Epstein-Barr Virus DNA in Burkitt’s Lymphomas and Nasopharyngeal Cancers 4 11. Papillomavirus Etiology of Cancer of the Cervix 6 111. Papillomaviruses in Nonanogenital Cancers 11 IV. Viruses as Tumor Initiators-Their Role as Inducers of Specific DNA Amplifications and as Mutagens 1 2 V. The Search for Other Tumorviruses 1 4 References 16 Signaling by the Cytokine Receptor Superfamily in Normal and Transformed Hematopoietlc Cells lames N . lhle 1. Introduction 23 11. Structure of the Cytokine Receptor Superfamily 24 111. Leukemic Transformation by Structurally Altered Cytokine Receptors 27 IV. Tyrosine Phosphorylation in Cytokine Receptor Function 2 9 V. Cytoplasmic Tyrosine Kinases Implicated in Specific Cytokine Responses 3 0 VI. /anus Kinases: A Unique Family of Cytoplasmic Protein Tyrosine Kinases 31 V11. Association of Jaks with Cytokine Receptors and Activation Following Ligand Binding 33 VIII. Activation of the ras Signaling Pathway by Cytokine Receptors 37 1X. Cytokine-Induced Increases in Phosphatidylinositol (PI) 3-Kinase Activity 3 9 X. Cytokine-Induced Tyrosine Phosphorylation of Vav 40 XI. Hematopoietic Cell Phosphatase: A Negative Growth Regulator 40 XII. Syp Tyrosine Phosphatase: A Positive Growth Regulator 4 2 XIII. IRS-1 and 4PS: Signal Transducers Phosphorylated in Response to Cytokines 4 2 V vi Contents XIV. Stats: A Novel Family of Transcription Factors Identified in Interferon Signaling 43 XV. Stats: A Common Theme in Cytokine Signaling 46 XVI. Mechanisms of Stat Recruitment to Cytokine Receptor Complexes 49 XVII. Concluding Remarks 50 References 5 1 Genetic Alterations of Cyclins, Cyclin-Dependent Kinases, a n d Cdk Inhibitors in Human Cancer Marcia Hall a n d G o r d o n Peters 1. Introduction 67 11. The Cell Cycle and Cancer 68 111. Chromosomal Translocations Affecting Cyclin D1 72 IV. Amplification of Cyclin D1 in Human Tumors 79 V. Amplification of Cdk4 in Sarcomas and Gliomas 89 VI. Deletion or Mutation of the p16/CDKN2 Gene in Primary Tumors VII. The Cyclin D1-pl6-pRb Pathway in Human Cancer 94 ' References 9 7 Myc Proteins: Essential Regulators of Cell Growth Marie Henriksson a n d Bernhard Luscher 1. Introduction 110 11. The myc Genes and Functional Domains of the Myc Proteins 111. The Myc Network 119 112 IV. Myc Target Genes 129 V. The Role of