Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-9-9
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3085-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12218125-5' Untranslated Regions, pubmed-meshheading:12218125-Animals, pubmed-meshheading:12218125-Antineoplastic Agents, Alkylating, pubmed-meshheading:12218125-B-Lymphocytes, pubmed-meshheading:12218125-Cell Differentiation, pubmed-meshheading:12218125-Clone Cells, pubmed-meshheading:12218125-DNA Methylation, pubmed-meshheading:12218125-Ethyl Methanesulfonate, pubmed-meshheading:12218125-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12218125-Gene Silencing, pubmed-meshheading:12218125-Genes, MHC Class II, pubmed-meshheading:12218125-Histocompatibility Antigens Class II, pubmed-meshheading:12218125-Hybridomas, pubmed-meshheading:12218125-Leukemia L1210, pubmed-meshheading:12218125-Mice, pubmed-meshheading:12218125-Mice, Inbred DBA, pubmed-meshheading:12218125-Nuclear Proteins, pubmed-meshheading:12218125-Promoter Regions, Genetic, pubmed-meshheading:12218125-Trans-Activators, pubmed-meshheading:12218125-Transcription, Genetic, pubmed-meshheading:12218125-Transfection, pubmed-meshheading:12218125-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.
pubmed:affiliation
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. shawn.murphy@roswellpark.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't