JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma.
High expression of CD30 and JunB is characteristic of tumor cells in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). Possible interactions of CD30 and JunB were examined in this study. We found that the CD30 promoter in tumor cells of both nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)-positive and NPM-ALK-negative ALCL and HL is regulated by a constitutively active CD30-extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK). Phosphorylation of ERK1/2 MAPK was confirmed in nuclei of tumor cells in both ALCL and HL. CD30-ERK1/2 MAPK signals induce JunB expression, which maintains high activity of the CD30 promoter. JunB induction seems to be largely independent of nuclear factor kappaB in ALCL and HL. These results show a common mechanism of CD30 overexpression in ALCL and HL, although the outcome of CD30 signaling differs between NPM-ALK-positive ALCL and NPM-ALK-negative ALCL, cutaneous ALCL, and HL as we recently reported.
Watanabe
Mariko
M
Fourth Department of Internal Medicine, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan.
Sasaki
Masataka
M
Itoh
Kinji
K
Higashihara
Masaaki
M
Umezawa
Kazuo
K
Kadin
Marshall E
ME
Abraham
Lawrence J
LJ
Watanabe
Toshiki
T
Horie
Ryouichi
R
D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006689:Hodgkin Disease / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D016539:Reed-Sternberg Cells / Q000201:enzymology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017730:Ki-1 Antigen; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases