Transactivation of the ICAM-1 gene by CD30 in Hodgkin's lymphoma.
The ICAM-1/LFA-1 complex mediates cell-cell interaction. ICAM-1 is overexpressed in Hodgkin/Reed-Sternberg (H/RS) cells, and serum levels of its soluble form are higher in Hodgkin's lymphoma (HL) patients than in controls. There are no data, however, regarding the regulation of expression of ICAM-1 in H/RS cells. CD30 was identified in H/RS cells of HL and has attracted much interest as a molecular marker of HL. To analyze ICAM-1 expression in H/RS cells, we examined the expression of ICAM-1, LFA-1, CD30 and CD30L in HL-derived cell lines. All cell lines expressed ICAM-1 and CD30, but not LFA-1 or CD30L. CD30 induced ICAM-1 expression. Analysis of the ICAM-1 promoter showed the importance of NF-kappaB binding site for CD30-induced ICAM-1 gene expression. Coexpression of IkappaB, IKK, NIK and TRAF dominant-negative constructs with CD30 inhibited CD30-induced activation of ICAM-1 promoter, suggesting that CD30 induces ICAM-1 via NF-kappaB signalling. The ICAM-1 promoter was activated by the C-terminal region of CD30, which activated NF-kappaB signalling. A decoy CD30 lacking the cytoplasmic region inhibited ICAM-1 promoter activity in HL cell lines. Thus, in H/RS cells, ligand-independent activation of CD30 signalling activates NF-kappaB and this leads to constitutive ICAM-1 expression, suggesting a link between 2 well known phenotypic characteristics of HL, CD30 and ICAM-1 overexpression.
Uchihara
Jun-Nosuke
JN
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
Matsuda
Takehiro
T
Okudaira
Taeko
T
Ishikawa
Chie
C
Masuda
Masato
M
Horie
Ryouichi
R
Watanabe
Toshiki
T
Ohta
Takao
T
Takasu
Nobuyuki
N
Mori
Naoki
N
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D053285:CD30 Ligand; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D017730:Ki-1 Antigen / Q000235:genetics / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D016328:NF-kappa B / Q000145:classification / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D053285:CD30 Ligand; D017730:Ki-1 Antigen; D016169:Lymphocyte Function-Associated Antigen-1; D016328:NF-kappa B; C505774:TNFSF8 protein, human; D048069:Tumor Necrosis Factors; D018799:Intercellular Adhesion Molecule-1