Ultraviolet irradiation, although it activates the transcription factor AP-1 in F9 teratocarcinoma stem cells, does not induce the full complement of differentiation-associated genes.
Induction of differentiation of F9 teratocarcinoma stem cells by retinoic acid and cAMP has been shown to involve the activation of the transcription factor AP-1 (a heterodimer of the proto-oncogene products c-Fos and c-Jun); moreover, stable expression of either Fos or Jun drives F9 cells into differentiation. Phorbol ester tumor promoters and short-wave-length ultraviolet (uv) irradiation are efficient inducers of AP-1 activity in various differentiated cells, but it has been shown that phorbol esters do not induce AP-1 activity in undifferentiated F9 cells. We examine here whether uv irradiation induces AP-1 activity in these cells and drives F9 cells into differentiation. We show that uv induces, in contrast to phorbol esters, the formation of active AP-1 by activating transcription from the c-jun gene. Ultraviolet-induced AP-1 drives transcription from AP-1-dependent promoters coding for differentiation-associated proteins (such as urokinase and keratin 18). However, in uv-treated cells, these genes are activated earlier and to a greater extent than in cells treated with retinoic acid and cAMP. More importantly, uv, in contrast to retinoic acid and cAMP, does not induce the accumulation of collagen alpha 1 (IV) and laminin B1 RNA. Our data suggest that the c-jun gene in F9 cells is accessible to immediate activation, but that uv-induced AP-1 activation does not suffice to induce the full program of F9 cell differentiation.
Auer
H P
HP
Kernforschungszentrum Karlsruhe, Institut für Genetik, Germany.
König
H
H
Litfin
M
M
Stein
B
B
Rahmsdorf
H J
HJ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003094:Collagen / Q000096:biosynthesis; D000242:Cyclic AMP / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D016758:Genes, jun; D007633:Keratins / Q000096:biosynthesis; D007797:Laminin / Q000096:biosynthesis; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism* / Q000528:radiation effects; D018243:Teratocarcinoma / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D007797:Laminin; D010703:Phorbol Esters; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014212:Tretinoin; D007633:Keratins; D003094:Collagen; D000242:Cyclic AMP; D014568:Urokinase-Type Plasminogen Activator