The expression of CD30 in anaplastic large cell lymphoma is regulated by nucleophosmin-anaplastic lymphoma kinase-mediated junB level in a cell type-specific manner

• Published in: Cancer research (Chicago, Ill.) Ill.), 2006-09, Vol.66 (18), p.9002-9008
• Main Authors: HSU, Faye Yuan-Yi, JOHNSTON, Patrick B, BURKE, Kathleen A, YI ZHAO
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Cell Growth Processes - physiology; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Silencing; Hematologic and hematopoietic diseases; Humans; Ki-1 Antigen - biosynthesis; Ki-1 Antigen - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Medical sciences; Pharmacology. Drug treatments; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - biosynthesis; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-jun - biosynthesis; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; RNA Interference; RNA, Small Interfering - genetics; Transcription, Genetic; Transcriptional Activation; Transfection; Tumors
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-05-4101

Chromosomal translocation t(2;5) and the resulting fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) are detected in 50% to 70% of anaplastic large cell lymphoma (ALCL), which is a T/null cell non-Hodgkin's lymphoma showing anaplastic morphology with cell surface expression of CD30. Because aberrant CD30 expression was also observed in the T-cell lymphoma derived from lineage-specific NPM-ALK transgenic mice, we tested the hypothesis that there might be a functional relationship between the two neoplastic-related proteins: NPM-ALK and CD30. In this study, we used the RNA interference method to modulate NPM-ALK protein expression in ALCL-derived, t(2;5)-positive Karpas 299 cells. We observed decreased CD30 expression when NPM-ALK was repressed. Further analysis suggested that JunB functioned as the mediator of NPM-ALK-derived CD30 transcriptional regulation. The NPM-ALK-repressed cells, which had low CD30 expression, were characterized with lower cell proliferation compared with cells in the control group, suggesting that altered CD30 expression may correlate to NPM-ALK-mediated tumor cell growth inhibition. Combination of NPM-ALK repression and CD30 ligand leads to significantly increased tumor cell growth inhibition compared with one method alone, suggesting its potential application for ALCL-specific cancer treatment.