The JI PBL Intereron Source
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murphy, S. P.
Right arrow Articles by Fuji, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murphy, S. P.
Right arrow Articles by Fuji, H.
The Journal of Immunology, 2002, 169: 3085-3093.
Copyright © 2002 by The American Association of Immunologists

DNA Alkylating Agents Alleviate Silencing of Class II Transactivator Gene Expression in L1210 Lymphoma Cells1

Shawn P. Murphy2, Renae Holtz, Nicole Lewandowski, Thomas B. Tomasi and Hiroshi Fuji

Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263

MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA). Analysis of stable hybrids suggests that CIITA expression is repressed by a dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA and class II expression in class II negative L1210 cells, and this effect appears to be restricted to transformed cell lines derived from the early stages of B cell ontogeny. Transient transfection assays demonstrated that the CIITA type III promoter is active in class II- L1210 cells, despite the fact that the endogenous gene is not expressed, which suggests that these cells have all of the transacting factors necessary for CIITA transcription. An inverse correlation between methylation of the CIITA transcriptional regulatory region and CIITA expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment activated CIITA expression in class II-negative L1210 cells. Collectively, our results suggest that 1) CIITA gene expression is repressed in class II- L1210 cells by methylation of the CIITA upstream regulatory region, and 2) treatment with DNA-alkylating agents overcomes methylation-based silencing of the CIITA gene in L1210 cells.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
T. M. Holling, M. W. T. Bergevoet, L. Wilson, M. C. J. A. Van Eggermond, E. Schooten, R. D. M. Steenbergen, P. J. F. Snijders, M. J. Jager, and P. J. Van den Elsen
A Role for EZH2 in Silencing of IFN-{gamma} Inducible MHC2TA Transcription in Uveal Melanoma
J. Immunol., October 15, 2007; 179(8): 5317 - 5325.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. M. Rimsza, R. A. Roberts, E. Campo, T. M. Grogan, S. Bea, I. Salaverria, A. Zettl, A. Rosenwald, G. Ott, H. K. Muller-Hermelink, et al.
Loss of major histocompatibility class II expression in non-immune-privileged site diffuse large B-cell lymphoma is highly coordinated and not due to chromosomal deletions
Blood, February 1, 2006; 107(3): 1101 - 1107.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S.-D. Chou, A. N. H. Khan, W. J. Magner, and T. B. Tomasi
Histone acetylation regulates the cell type specific CIITA promoters, MHC class II expression and antigen presentation in tumor cells
Int. Immunol., November 1, 2005; 17(11): 1483 - 1494.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. P. Dunn, K. C.F. Sheehan, L. J. Old, and R. D. Schreiber
IFN Unresponsiveness in LNCaP Cells Due to the Lack of JAK1 Gene Expression
Cancer Res., April 15, 2005; 65(8): 3447 - 3453.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
R. Holtz, J. C. Choi, M. G. Petroff, J. F. Piskurich, and S. P. Murphy
Class II Transactivator (CIITA) Promoter Methylation Does Not Correlate with Silencing of CIITA Transcription in Trophoblasts
Biol Reprod, September 1, 2003; 69(3): 915 - 924.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. J. van den Elsen, N. van der Stoep, and T. Yazawa
Class II Transactivator (CIITA) Deficiency in Tumor Cells: Complicated Mechanisms or Not?
Am. J. Pathol., July 1, 2003; 163(1): 373 - 376.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Kanaseki, H. Ikeda, Y. Takamura, M. Toyota, Y. Hirohashi, T. Tokino, T. Himi, and N. Sato
Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas
J. Immunol., May 15, 2003; 170(10): 4980 - 4985.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.