Expression of SET is modulated as a function of cell proliferation

We explored a biological role of SET as it relates to cell proliferation an d differentiation. Immunohistochemical staining demonstrated that the expre ssion of SET was ubiquitous and diffuse over the whole embryo on gestationa l day 15. At a later stage of development, SET was expressed at relatively lower levels and localized to specific tissues and cells. On embryonic day 19, specific SET immunoreactivity was found in the epithelium of skin, resp iratory tract, intestine, and retina as well as in muscle and cartilage. In these cells SET was stained mostly in the nucleus, which was supported ind irectly by nuclear transport of enhanced green fluorescence protein-SET fus ion proteins in ECV304 endothelial cells. Set mRNA expression was further c onfirmed in various cultured cells, including NIH 3T3 cells L6 myoblast cel ls, human umbilical vein endothelial cells, and ECV304 cells. Using F9 tera tocarcinoma cell lines, which were stimulated to differentiate into the two different cell lineages of parietal and visceral endoderm, we have further examined the role of SET. The expression of set mRNA and SET protein was d iminished about three-fold in both differentiated endoderm cells compared t o the undifferentiated F9 cells. However, when F9 cells were subjected to s erum starvation, reduction of set mRNA abundance also took place at a simil ar level to that observed in response to differentiation. Consistent with t his, quiescent L6 myoblast showed a marked down regulation of set mRNA comp ared to proliferating cells. These results suggest that SET is involved mai nly in the regulation of cell proliferation rather than differentiation dur ing embryonic development. J. Cell. Biochem. 74:119-126, 1999. (C) 1999 Wil ey-Liss, Inc.