High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma

Abstract We surveyed IL-21 receptor (IL-21R) in leukemia and lymphoma and found that follicular lymphoma cells showed exceptionally high IL-21R expression. Notably, IL-21 showed divergent effects depending on the cell origin: growth stimulation in Burkitt lymphoma cell lines and adult T cell leukemi...

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Veröffentlicht in:	Cancer letters 2007-10, Vol.256 (2), p.196-206
Hauptverfasser:	Akamatsu, Norihiko, Yamada, Yasuaki, Hasegawa, Hiroo, Makabe, Koki, Asano, Ryutaro, Kumagai, Izumi, Murata, Ken, Imaizumi, Yoshitaka, Tsukasaki, Kunihiro, Tsuruda, Kazuto, Sugahara, Kazuyuki, Atogami, Sunao, Yanagihara, Katsunori, Kamihira, Shimeru
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis Apoptosis - drug effects Bcl-2 bcl-2-Associated X Protein - metabolism Caspase 3 - metabolism Caspase 8 - metabolism Cell growth Cell Proliferation - drug effects Dose-Response Relationship, Drug Enzyme Activation Flow cytometry Follicular lymphoma Hematology, Oncology and Palliative Medicine Humans IL-21 Interleukins - metabolism Interleukins - pharmacology Interleukins - therapeutic use Jurkat Cells K562 Cells Kinases Leukemia Leukemia - drug therapy Leukemia - enzymology Leukemia - metabolism Leukemia - pathology Lymphocytes Lymphoma Lymphoma, Follicular - drug therapy Lymphoma, Follicular - enzymology Lymphoma, Follicular - metabolism Lymphoma, Follicular - pathology Membrane Potential, Mitochondrial Proto-Oncogene Proteins c-bcl-2 - metabolism Receptors, Interleukin-21 - metabolism Recombinant Proteins - metabolism Signal Transduction - drug effects Time Factors Tumor Cells, Cultured Tumors U937 Cells
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Zusammenfassung:	Abstract We surveyed IL-21 receptor (IL-21R) in leukemia and lymphoma and found that follicular lymphoma cells showed exceptionally high IL-21R expression. Notably, IL-21 showed divergent effects depending on the cell origin: growth stimulation in Burkitt lymphoma cell lines and adult T cell leukemia/lymphoma cell lines but induction of apoptosis in B lymphoma cell lines with t(14;18)(q32;q21), a marker karyotype of follicular lymphoma. IL-21 activated caspase-8 and -3 and reduced mitochondrial membrane potential. More importantly, IL-21 decreased Bcl-2 expression but increased Bax expression. These results support a new therapeutic approach using the IL-21/IL-21R system in follicular lymphoma.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2007.06.001