Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease.
Immunoglobulin transcription is impaired in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD). We recently demonstrated that defective immunoglobulin promoter transcription correlates with the down-regulation of the B-cell transcription factors Oct2 and BOB.1/OBF.1. These results prompted us to investigate whether immunoglobulin enhancer activity is also impaired in HRS cells and whether as yet unidentified factors could be necessary for immunoglobulin enhancer activity in HRS cells of cHD. Here we analyzed 30 cases of cHD for expression of the Ets family member PU.1 that is known to collaborate with multiple transcription factors and to regulate expression of immunoglobulin genes. We show that PU.1 is not expressed in primary and cultured HRS cells. Reintroduction of PU.1 and Oct2 in cultured HRS cells restored the activity of cotransduced immunoglobulin enhancer constructs. Our study identifies PU.1 deficiency as a recurrent defect in HRS cells that might contribute to their impairment of immunoglobulin transcription.
Jundt
Franziska
F
Charité, Robert-Rössle-Klinik, Humboldt University of Berlin, Germany. fjundt@mdc-berlin.de
Kley
Katharina
K
Anagnostopoulos
Ioannis
I
Schulze Pröbsting
Kristina
K
Greiner
Axel
A
Mathas
Stephan
S
Scheidereit
Claus
C
Wirth
Thomas
T
Stein
Harald
H
Dörken
Bernd
B
D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D015536:Down-Regulation; D005803:Genes, Immunoglobulin / Q000187:drug effects; D006689:Hodgkin Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000187:drug effects / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D050813:Octamer Transcription Factor-2; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C091546:POU2AF1 protein, human; C058435:POU2F2 protein, human