Microgravity decreases c-fos induction and serum response element activity.
Several studies have shown that altered gravity conditions influence mammalian cell growth and differentiation. The molecular mechanisms underlying these effects, however, remain relatively obscure. In this paper we show that microgravity reached in a sounding rocket strongly decreases epidermal growth factor (EGF)-induced expression of the proto-oncogenes c-fos and c-jun, which are both implicated in the regulation of proliferation and differentiation. Decreased activity of the serum response element (SRE), present in the c-fos promoter-enhancer region, is probably responsible for the decrease in EGF-induced c-fos expression. In addition, we show that gravity alterations differentially modulate distinctive signal transduction pathways, indicating that gravity-dependent modulations of mammalian cell proliferation are unlikely to be caused by a nonspecific stress response of the cell.
de Groot
R P
RP
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Rijken
P J
PJ
den Hertog
J
J
Boonstra
J
J
Verkleij
A J
AJ
de Laat
S W
SW
Kruijer
W
W
D015152:Blotting, Northern; D004273:DNA, Neoplasm / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006112:Gravitation; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011519:Proto-Oncogenes / Q000187:drug effects / Q000502:physiology*; D012334:RNA, Neoplasm / Q000302:isolation & purification; D012260:Ribonucleases / Q000037:antagonists & inhibitors; D026362:Serum Response Factor; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D026362:Serum Response Factor; D004815:Epidermal Growth Factor; D012260:Ribonucleases