Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic large cell lymphoma
| Autor: | Masaaki Higashihara, Tukasa Koiwa, Marshall E. Kadin, Isao Okayasu, Mariko Watanabe, Toshiki Watanabe, Yuji Ogawa, Kinji Itoh, Ryouichi Horie |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CD30
Proto-Oncogene Proteins c-jun JUNB Molecular Sequence Data Ki-1 Antigen Biology Cell Line Pathology and Forensic Medicine immune system diseases hemic and lymphatic diseases medicine Humans Promoter Regions Genetic Molecular Biology Anaplastic large-cell lymphoma DNA Primers Base Sequence integumentary system Reverse Transcriptase Polymerase Chain Reaction Large cell DNA Cell Biology Methylation DNA Methylation Blotting Northern medicine.disease Hodgkin Disease Immunohistochemistry Lymphoma CpG site DNA methylation Cancer research Lymphoma Large-Cell Anaplastic CpG Islands |
| Zdroj: | Laboratory Investigation. 88:48-57 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.3700696 |
| Popis: | High expression of CD30 and JunB is the hallmark of malignant cells in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Ligand-independent signaling by CD30 induces JunB, which activates the CD30 promoter, stabilizing CD30 expression and supporting the survival of Hodgkin-Reed-Sternberg (H-RS) and ALCL cells. Here we show for the first time CpG islands encompassing 60 CpG dinucleotides, located in the core promoter, exon 1 and intron 1 of CD30 gene. Analysis of the methylation status of CD30 CpG islands in H-RS, ALCL and unrelated cell lines reveals an inverse relationship between the extent of CD30 CpG methylation and CD30 expression. CD30 CpG islands of H-RS and ALCL cell lines are rarely methylated. Methylation of the CD30 promoter decreases CD30 induction and JunB action on the demethylated CD30 promoter enhances CD30 induction. CD30 and JunB are strongly expressed in H-RS and ALCL cells, whereas they are not expressed in nonmalignant lymphocytes in which CD30 CpG islands are rarely methylated. We conclude that constitutive action of aberrantly expressed JunB on hypomethylated CD30 CpG islands of lymphocytes triggers CD30 induction and initiates activation of the JunB-CD30-JunB loop, essential to the pathogenesis of HL and ALCL. |
| Databáze: | OpenAIRE |
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