Classical Hodgkin lymphoma is characterized by high constitutive expression of activating transcription factor 3 (ATF3), which promotes viability of Hodgkin/Reed-Sternberg cells.
Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) display unique characteristics that discriminate cHL from other B-cell lymphomas and normal B cells. Therefore, comparative gene expression profiling of Hodgkin and non-Hodgkin B cells could lead to the identification of candidate genes that are critical for the pathogenesis of cHL. We performed microarray analysis of Hodgkin and non-Hodgkin cell lines and identified activating transcription factor 3 (ATF3), a member of the cyclic AMP response element binding protein (CREB)/ATF family, as a differentially expressed candidate gene. Extensive analysis of a large panel of cell lines, primary tumor samples, and normal tissues revealed that high expression of ATF3 is found in nearly all cases of cHL and is almost exclusively restricted to it. Selective knock-down of ATF3 by RNA interference suppressed proliferation and strongly reduced viability of Hodgkin cells. Thus, overexpression of ATF3 is a molecular hallmark of cHL that contributes to the malignant growth of HRS cells.
Janz
Martin
M
Hematology, Oncology, and Tumorimmunology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str 10, 13092 Berlin, Germany. mjanz@mdc-berlin.de
Hummel
Michael
M
Truss
Matthias
M
Wollert-Wulf
Brigitte
B
Mathas
Stephan
S
Jöhrens
Korinna
K
Hagemeier
Christian
C
Bommert
Kurt
K
Stein
Harald
H
Dörken
Bernd
B
Bargou
Ralf C
RC
D051700:Activating Transcription Factor 3 / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology*
D051700:Activating Transcription Factor 3; D034741:RNA, Small Interfering