CD56 expression in human myeloma cells derived from the neurogenic gene expression: possible role of the SRY-HMG box gene, SOX4.
CD56 is frequently detected on primary myeloma cells from more than 80% patients with overt myeloma. In order to clarify the possible mechanisms of CD56 expression in human myeloma, we underwent screening for potential targets by microarray analysis, where the CD56(+) myeloma cell lines showed markedly increased expressions of transcription factors involved in the neuronal cell lineage compared to the CD56(-) myeloma cell lines. Here, we show that among the SOX family of transcription factors, SOX4 was highly up-regulated and SOX1 was down-regulated in the CD56(+) myeloma cell lines as well as in primary myeloma cases as confirmed by the RT-PCR. ChIP analysis of the CD56 promoter region showed specific bindings of SOX4 in the CD56(+) and SOX1 in the CD56(-) myeloma cell lines, respectively. shRNA against SOX1 failed to induce CD56 expression in CD56(-) myeloma cell line, U266. On the contrary, over-expression of SOX4 in the CD56(-) myeloma cell line could induce the CD56 expression. Silencing of SOX4 by shRNA transfection down-regulated CD56 expression and induced apoptosis to CD56(+) human myeloma cell line, AMO1. Thus, induction of SOX4 gene expression might be responsible for the CD56 expression in human myeloma cells.
Iqbal
Mohd S
MS
Laboratory of Cellular Signal Analysis, Department of Bio-Signal Analysis, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan. iqbal@yamaguchi-u.ac.jp
Otsuyama
Ken-ichiro
K
Shamsasenjan
Karim
K
Asaoku
Hideki
H
Kawano
Michio M
MM
D019002:CD56 Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology*; D055495:Neurogenesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000502:physiology; D034741:RNA, Small Interfering; D055751:SOXC Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
D019002:CD56 Antigen; D034741:RNA, Small Interfering; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors