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.