help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watanabe, M.
Right arrow Articles by Horie, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, M.
Right arrow Articles by Horie, R.
(American Journal of Pathology. 2003;163:633-641.)
© 2003 American Society for Investigative Pathology

AP-1 Mediated Relief of Repressive Activity of the CD30 Promoter Microsatellite in Hodgkin and Reed-Sternberg Cells

Mariko Watanabe*, Yuji Ogawa*{dagger}, Kinji Ito{dagger}{ddagger}, Masaaki Higashihara*, Marshall E. Kadin§, Lawrence J. Abraham, Toshiki Watanabe{dagger} and Ryouichi Horie*{dagger}

From the Fourth Department of Internal Medicine,* Kitasato University School of Medicine, Kanagawa, Japan; the Department of Cancer Research,{dagger} Division of Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; the Department of Pathology,{ddagger} Toho University School of Medicine, Tokyo, Japan; the Department of Pathology,§ Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts; and the Department of Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences, University of Western Australia, Crawley, Australia

Overexpression of CD30 is the hallmark of Hodgkin and Reed-Sternberg (H-RS) cells and drives constitutive nuclear factor-{kappa}B activation that is the molecular basis for the pathophysiology of Hodgkin’s lymphoma. Transcription of the CD30 gene is controlled by the core promoter that is driven by Sp-1 and the microsatellite sequences (MSs) that represses core promoter activity. To understand the mechanism(s) of CD30 overexpression in H-RS cells, we structurally and functionally characterized the CD30 MSs. Although the CD30 MS of H-RS cell lines was polymorphic, it was not truncated compared with that of control cells. A strong core promoter activity and constitutive Sp-1 binding were revealed in all cell lines examined irrespective of the levels of CD30 expression. In transient reporter gene assays, all MS clones derived from H-RS cell lines repressed the core promoter activity in unrelated cell lines, but not in the H-RS cell lines. An AP-1-binding site was found in the MS at nucleotide position of -377 to -371, the presence of which was found to relieve repression of the core promoter in H-RS cell lines but not in other tumor cell lines. H-RS cell lines showed constitutive and strong AP-1-binding activity, but other cell lines did not. The AP-1 complex contained JunB, whose overexpression activated reporter constructs driven by the CD30 promoter including the MSs, and was dependent on the AP-1 site. JunB expression was detected in H-RS cells in vitro and in vivo, but not in reactive cells or tumor cells of non-Hodgkin’s lymphoma of diffuse large B-cell type. Transduction of JunB small interfering RNAs suppressed CD30 promoter activity in L428 cells but not in control cells. Taken together, overexpression and binding of JunB to the AP-1 site appear to relieve the repression of the core promoter by the CD30 MS in H-RS cells, which provide one basis for the constitutive overexpression of CD30 in Hodgkin’s lymphoma.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
F. Y.-Y. Hsu, P. B. Johnston, K. A. Burke, and Y. Zhao
The Expression of CD30 in Anaplastic Large Cell Lymphoma Is Regulated by Nucleophosmin-Anaplastic Lymphoma Kinase-Mediated JunB Level in a Cell Type-Specific Manner.
Cancer Res., September 15, 2006; 66(18): 9002 - 9008.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Ebersole, Y. Okamoto, V. N. Noskov, N. Kouprina, J.-H. Kim, S.-H. Leem, J. C. Barrett, H. Masumoto, and V. Larionov
Rapid generation of long synthetic tandem repeats and its application for analysis in human artificial chromosome formation
Nucleic Acids Res., September 1, 2005; 33(15): e130 - e130.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Watanabe, M. Sasaki, K. Itoh, M. Higashihara, K. Umezawa, M. E. Kadin, L. J. Abraham, T. Watanabe, and R. Horie
JunB Induced by Constitutive CD30-Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase Signaling Activates the CD30 Promoter in Anaplastic Large Cell Lymphoma and Reed-Sternberg Cells of Hodgkin Lymphoma
Cancer Res., September 1, 2005; 65(17): 7628 - 7634.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Imamura, C. Imamura, Y. Iwamoto, and L. J. Sandell
Transcriptional Co-activators CREB-binding Protein/p300 Increase Chondrocyte Cd-rap Gene Expression by Multiple Mechanisms Including Sequestration of the Repressor CCAAT/Enhancer-binding Protein
J. Biol. Chem., April 29, 2005; 280(17): 16625 - 16634.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.