期刊
ONCOTARGET
卷 4, 期 7, 页码 1008-1018出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1049
关键词
SILAC; quantitative proteomics; oncotargets; multiple myeloma
资金
- National Medical Research Council of Singapore [NMRC/EDG/2010/1004]
- NMRC Clinician Scientist Investigator award
- Singapore Cancer Syndicate Grant
- Singapore National Research Foundation
- Ministry of Education under the Research Centre of Excellence Programme
Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. MMSET, identified by its fusion to the IgH locus in t(4;14) MM, is universally overexpressed in t(4; 14) MM. In order to identify cell surface biomarkers associated with t(4; 14) MM for small molecule or antibody based therapies, we knocked down MMSET expression with shRNA and generated a cell line pair from KMS11, a t(4; 14) MM cell line. We used quantitative mass spectrometry to identify plasma membrane proteins associated with MMSET overexpression. Using this approach, 50 cell surface proteins were identified as differentially expressed between KMS11 and KMS11/shMMSET. Western blot and flow cytometry analysis indicated SLAMF7 was overexpressed in t(4; 14) MM cell lines and down-regulated by MMSET shRNAs. SLAMF7 expression was also confirmed in primary t(4; 14) MM samples by flow cytometry analysis. Quantitative RT-PCR and ChIP analysis indicated MMSET might regulate the transcription level of SLAMF7 and be an important functional element for SLAMF7 promoter activity. Furthermore, SLAMF7 shRNA could induce G1 arrest or apoptosis and reduce clonogenetic capacity in t(4; 14) MM cells. Overall, these results illustrated SLAMF7 might be a novel cell surface protein associated with t(4; 14) MM. It is potential to develop t(4; 14) MM targeted therapy by SLAMF7 antibody mediated drug delivery.
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