Absence of T-cell- and B-cell-specific transcription factors TCF-1, GATA-3, and BSAP in Hodgkin's Reed-Sternberg cells.
Based on the presence of T cell receptor-beta (TcR-beta) gene rearrangements in L428 and HDLM-1 cells, the expression of CD2 in HDLM-1 cells, and the presence of immunoglobulin heavy-chain (IgH) gene rearrangement in KM-H2 cells, some researchers have concluded that these long-term cell lines derived from patients with Hodgkin's disease are lymphoid in nature. The information obtained from these cell lines has also been used in arguments for a lymphoid origin of H-RS cells in tissue despite the frequent absence of lymphoid markers and Ig/TcR gene rearrangements in these cells. We questioned whether one can use the limited expression of lymphoid markers or the limited gene rearrangement to conclude that H-RS cells have a lymphoid origin, because these markers may be aberrant in tumor cells. In this study, we examined the expression of two T-cell-specific transcription factors (TCF-1 and GATA-3) and one B-cell-specific transcription factor (BSAP) in cultured H-RS cells by using a gel mobility shift assay. The sensitivity and specificity of this assay for determination of cell lineage have been established in a large number of cultured human and murine cell lines. All three types of H-RS cell lines were consistently negative for BSAP, TCF-1, and GATA-3. The absence of GATA-3 was confirmed in H-RS cells in tissues by an in situ hybridization technique. Virtually all B-cell lines, with the exception of some myeloma cell lines, are positive for BSAP, which is the transcription factor for promoters for several B-cell markers, including VpreB1, lambda 5, CD19, and CD20. All T-cell lines tested were positive for TCF-1 and GATA-3, which are the transcription factors for promoters for several T-cell-restricted markers, including CD2, CD3, TcR, and lck. The absence of BSAP, TCF-1, and GATA-3 clearly indicates an underlying difference between H-RS cells and lymphoid cells.
Hsu
P L
PL
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Xie
S S
SS
Hsu
S M
SM
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D050990:GATA3 Transcription Factor; D005838:Genotype; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D051757:PAX5 Transcription Factor; D010641:Phenotype; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000502:physiology; D012680:Sensitivity and Specificity; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D015335:Molecular Probes; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D015534:Trans-Activators; D014157:Transcription Factors