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Gene Expression By Single Reed-Sternberg Cells: Pathways Of Apoptosis And Activation
Christina Messineo, M. H. Jamerson, E. Hunter, R. Braziel, A. Bagg, S. G. Irving, J. Cossman
Published 1998 · Biology
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Although Hodgkin's disease is highly responsive to treatments that cause apoptosis, it remains resistant to the physiological mechanisms intended to cause cell death. Presumably, the Reed-Sternberg cell defies endogenous apoptosis, persists, accumulates, and manifests the malignant disorder seen clinically. The Reed-Sternberg cell expresses several members of the tumor necrosis factor receptor superfamily. This family of receptors is involved in both activation and proliferation of cells, as well as either protection from or initiation of apoptosis in cells expressing these surface proteins. Signals from these receptors affect transcription. We reasoned that the activation state and resistance to apoptosis of Reed-Sternberg cells might be attributable to dysregulation of genes controling these processes. To determine gene expression by Reed-Sternberg cells, we developed a method of micromanipulation, global reverse transcription, and the reverse transcription-polymerase chain reaction and applied it to 51 single Reed-Sternberg cells and their variants from six cases of Hodgkin's disease. This report analyzes the gene expression of bcl-xs , bcl-xl , bax -α, bax -β, fadd , fas , fas ligand ( fas L ), ice , TNF -α, TNF -β, TNFR1 , TNFR2 , TRAF1 , TRAF2 , TRAF3 , cIAP2 , and tradd at the level of mRNA in the single Reed-Sternberg cells and their variants. The findings here suggest a molecular mechanism for the activated state and in vivo survival occurring in untreated Reed-Sternberg cells of Hodgkin's disease.
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