High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells.
There is a considerable lack of understanding about the common molecular defects that form the basis for the occurrence of Hodgkin's lymphoma. Despite a number of molecular tools used thus far in immunophenotypic and karyotypic studies, it has not been possible to establish a single common trait among various Hodgkin (H)-cell lines or primary tumor cells that would allow classification into a particular hematopoietic lineage. With this study, we demonstrate that a characteristic expression pattern of transcription factors provides a unifying principle. Seven different cell lines derived from patients with Hodgkin's disease (HD), as well as primary H/Reed-Sternberg (RS) cells isolated from the pericardial fluid of a patient with HD, were compared with a number of hematopoietic and nonhematopoietic cell lines for the expression of Oct-2, a tissue-specific transcription factor normally restricted to B cells, and nuclear factor kappa B (NF-kappa B), an inducible transcription factor. Regardless of the heterogeneous phenotypes and genotypes of the H cell lines, which varied inconsistently between B-cell-, T-cell-, or monocyte-like properties, all H cells tested displayed expression of Oct-2 protein at levels comparable to those seen in B cells. Furthermore, all cell lines showed an abundant constitutive nuclear NF-kappa B activity. Interestingly, anaplastic large-cell lymphoma (ALCL) cell lines, which have many features in common with H/RS cells, were devoid constitutive nuclear NF-kappa B activity. Unlike the constitutive NF-kappa B activity known for B cells, which mainly consists of the p50 and c-Rel or RelB subunits, we demonstrate by antibody supershifting experiments that H cells contain constitutive nuclear p50 and p65, the dimeric NF-kappa B normally observed only for limited time intervals after stimulation with diverse inducers. Additionally, some H-cell lines also displayed nuclear c-Rel activity, whereas RelB or p52 were not detected as part of the constitutive activity. The expression pattern of Oct-2 and NF-kappa B appears to be a unifying and characteristic property of H cells and might explain the deregulated expression of various cytokines leading to the clinical and pathologic manifestations of HD.
Bargou
R C
RC
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Leng
C
C
Krappmann
D
D
Emmerich
F
F
Mapara
M Y
MY
Bommert
K
K
Royer
H D
HD
Scheidereit
C
C
Dörken
B
B
D001402:B-Lymphocytes / Q000473:pathology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D050813:Octamer Transcription Factor-2; D010954:Plasmacytoma / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D013601:T-Lymphocytes / Q000473:pathology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D050813:Octamer Transcription Factor-2; C058435:POU2F2 protein, human; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors