Expression of Dual-Specificity Phosphatase 5 Pseudogene 1 DUSP5P1 in Tumor CellsReport as inadecuate

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Sequencing of individual clones from a newly established cDNA library from the chemoresistant Hodgkin-s lymphoma cell line L-1236 led to the isolation of a cDNA clone corresponding to a short sequence from chromosome 1. Reverse transcriptase-polymerase chain reaction indicated high expression of this sequence in Hodgkin-s lymphoma derived cell lines but not in normal blood cells. Further characterization of this sequence and the surrounding genomic DNA revealed that this sequence is part of a human endogenous retrovirus locus. The sequence of this endogenous retrovirus is interrupted by a pseudogene of the dual specificity phosphatase 5 DUSP5. Reverse transcriptase-polymerase chain reaction revealed high expression of this pseudogene DUSP5P1 in HL cell lines but not in normal blood cells or Epstein-Barr virus-immortalized B cells. Cells from other tumor types Burkitt-s lymphoma, leukemia, neuroblastoma, Ewing sarcoma also showed a higher DUSP5P1-DUSP5 ratio than normal cells. Furthermore, we observed that higher expression of DUSP5 in relation to DUSP5P1 correlated with the expression of the pro-apoptotic factor B cell leukemia-lymphoma 2-like 11 BCL2L11 in peripheral blood cells and HL cells. Knock-down of DUSP5 in HL cells resulted in down-regulation of BCL2L11. Thus, the DUSP5-DUSP5P1 system could be responsible for regulation of BCL2L11 leading to inhibition of apoptosis in these tumor cells.

Author: Martin S. Staege , Katja Müller, Stefanie Kewitz, Ines Volkmer, Christine Mauz-Körholz, Toralf Bernig, Dieter Körholz



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