Molecular Mechanism of CD56 Expression in Human Myeloma Cells

Abstract

CD56 (NCAM1), one of the non-B cell lineage markers, is frequently detected on primary myeloma cells from more than 80% patients with overt myeloma. Microarray analysis of 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. There are three important binding sites of transcription factors such as HOX, SOX and PAX, present in the CD56 promoter region. Furthermore, ChIP analysis showed the specific bindings of HOXB9 and SOX1 in the CD56 promoter region of both the CD56(+) and CD56(−) myeloma cell line, while there was no significant difference observed in the PAX8 expression between the CD56(+) and CD56(−) myeloma cell lines. RT-PCR and western blot analysis confirmed that HOXB3 and HOXB9 as well as some of their potential cofactors were up-regulated in the CD56(+) myeloma cell lines with the concomitant down-regulation of the SOX1 and OCT3/4. First, we focused on the role of down-regulation of SOX1 in the CD56(−) myeloma cell line by the shRNA transfection. However, shRNA against SOX1 failed to induce CD56 expression in CD56(−) myeloma cell line. Therefore, these results indicate that the down-regulation of SOX1 alone may not be enough for the CD56 induction which might also require the overexpression of either HOXB9 or HOXB3, and the further study in the molecular mechanism of CD56 expression might contribute to the understanding of complex network of the interaction of transcription factors in human myeloma cells.