RRC ID 35748
Author Hiratsuka T, Takei Y, Ohmori R, Imai Y, Ozeki M, Tamaki K, Haga H, Nakamura T, Tsuruyama T.
Title ZFP521 contributes to pre-B-cell lymphomagenesis through modulation of the pre-B-cell receptor signaling pathway.
Journal Oncogene
Abstract ZFP521 was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521 to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521 in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521 was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTK and BANK1 were positively regulated by the ZFP521 gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-myc and c-jun were upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-myc and c-jun and of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTK and BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521 in humans, was upregulated. In conclusion, our data showed that the ZFP521 gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.
Volume 35(25)
Pages 3227-38
Published 2016-6-23
DOI 10.1038/onc.2015.385
PII onc2015385
PMID 26522721
MeSH Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Agammaglobulinaemia Tyrosine Kinase Animals Cell Line Cell Proliferation / genetics Cyclin D3 / genetics Cyclin D3 / metabolism Disease Models, Animal Gene Expression Regulation Humans Immunoblotting Immunohistochemistry Mice, Inbred C57BL Mice, Inbred Strains Pre-B Cell Receptors / genetics Pre-B Cell Receptors / metabolism* Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism* Precursor Cells, B-Lymphoid / metabolism* Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism Proto-Oncogene Proteins c-jun / genetics Proto-Oncogene Proteins c-jun / metabolism Proto-Oncogene Proteins c-myc / genetics Proto-Oncogene Proteins c-myc / metabolism RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics Transcription Factors / genetics Transcription Factors / metabolism*
IF 7.971
Times Cited 11
Mice RBRC00222