Early hematopoietic zinc finger protein prevents tumor cell recognition by natural killer cells Journal Article
| Authors: | La Rocca, R.; Fulciniti, M.; Lakshmikanth, T.; Mesuraca, M.; Ali, T. H.; Mazzei, V.; Amodio, N.; Catalano, L.; Rotoli, B.; Ouerfelli, O.; Grieco, M.; Gulletta, E.; Bond, H. M.; Morrone, G.; Ferrone, S.; Carbone, E. |
| Article Title: | Early hematopoietic zinc finger protein prevents tumor cell recognition by natural killer cells |
| Abstract: | Early hematopoietic zinc finger/zinc finger protein 521 (EHZF/ZNF521) is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is down-regulated during their differentiation. Its transcript is also abundant in some hematopoietic malignancies. Analysis of the changes in the antigenic profile of cells transfected with EHZF cDNA revealed up-regulation of HLA class I cell surface expression. This phenotypic change was associated with an increased level of HLA class I H chain, in absence of detectable changes in the expression of other Ag-processing machinery components. Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9. Preincubation of transfected cells with HLA class I Ag-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I Ag up-regulation in the NK resistance induced by EHZF. A potential clinical significance of these findings is further suggested by the inverse correlation between EHZF and MHC class I expression levels, and autologous NK susceptibility of freshly explanted multiple myeloma cells. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | clinical article; controlled study; unclassified drug; dna binding protein; human cell; genetics; dna-binding proteins; nonhuman; protein function; neoplasm; neoplasms; animal cell; animal; metabolism; animals; cancer susceptibility; multiple myeloma; gene expression; cell line; down-regulation; genetic transcription; transcription, genetic; hela cell; cercopithecus aethiops; monoclonal antibody; antigen presentation; immunology; genetic transfection; antigen recognition; hla antigen class 1; histocompatibility antigens class i; tumor cell; ligand; cercopithecus; transgene; ligands; natural killer cell; killer cells, natural; down regulation; upregulation; up-regulation; zinc finger protein; phenotypic variation; transgenes; complementary dna; early hematopoietic zinc finger protein; zinc finger protein 521, human; lymphoblastoid cell line; natural killer cell mediated cytotoxicity; uterine cervix carcinoma |
| Journal Title: | Journal of Immunology |
| Volume: | 182 |
| Issue: | 8 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-04-15 |
| Start Page: | 4529 |
| End Page: | 4537 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0802109 |
| PUBMED: | 19342626 |
| PROVIDER: | scopus |
| PMCID: | PMC2747523 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
