Retinoic acid induces activin receptor IIB mRNA in F9 embryonal carcinoma cells.
Mouse embryonal carcinoma F9 cells are pluripotent stem cells and differentiate into primitive endodermal cells upon treatment with retinoic acid (RA). We have recently shown that in F9 cells RA regulates gene expression of activin receptor type II (ActR-II), whose ligand is a potent differentiation agent. The present study examined the regulation of the newly cloned activin receptor type IIB (ActR-IIB) gene by RA. F9 cells expressed equal amounts of three ActR-IIB transcripts of 8.0, 7.5 and 4.0 kb. Both 9-cis-RA (c-RA) and all-trans-RA (t-RA) induced ActR-IIB gene expression in a dose-dependent manner. At 10(-9) M c-RA exerted no effect, while 10(-5) M c-RA increased the 8.0 kb ActR-IIB transcript about sevenfold. In contrast, t-RA induced the 8.0 kb ActR-IIB transcript fivefold at 10(-9) M and up to eightfold at 10(-5) M. The inductive effect on the 8.0 kb transcript was greater than that on the 7.5 kb transcript, and was least effective on the 4.0 kb transcript, suggesting that these three mRNA isoforms may originate from different promoters. Both cycloheximide and actinomycin D inhibited the inductive effect of t-RA on ActR-IIB gene expression, in contrast to ActR-II whose gene expression was not suppressed by cycloheximide but abolished by actinomycin D. Thus, endodermal differentiation of F9 cells is associated with activation of ActR-IIB gene and the mechanisms involved in the regulation of ActR-II and IIB gene expression are different.
Wan
Y J
YJ
Department of Pathology, Harbor UCLA Medical Center, Torrance 90509, USA.
Wang
L
L
Wu
T C
TC
D029404:Activin Receptors; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004707:Endoderm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D018243:Teratocarcinoma / Q000235:genetics / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*
D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D014212:Tretinoin; D029404:Activin Receptors